Can neostigmine cause muscle twitches?

Can Neostigmine Cause Muscle Twitches?

Yes, neostigmine can cause muscle twitches and fasciculations, particularly when administered inappropriately or in excessive doses, due to its mechanism as an acetylcholinesterase inhibitor that increases acetylcholine concentration at the neuromuscular junction. 1

Mechanism of Muscle Twitching with Neostigmine

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 This mechanism is similar to organophosphate pesticides and chemical nerve agents like sarin, which also produce fasciculations through unopposed acetylcholine action at nicotinic receptors. 1

Clinical Contexts Where Muscle Twitching Occurs

When Administered Without Residual Blockade

Administering neostigmine when the train-of-four (TOF) ratio is already ≥0.9 (no residual blockade) can paradoxically impair neuromuscular transmission and cause muscle weakness rather than typical fasciculations. 1, 2 Specifically:

• Neostigmine 40 mcg/kg given when TOF ratio >0.9 may decrease the TOF ratio and impair neuromuscular function for 17-52 minutes 1
• This represents a depolarizing-type blockade rather than classic fasciculations 3

Excessive Dosing

Large doses of neostigmine administered when neuromuscular blockade is minimal can produce neuromuscular dysfunction, including muscle twitching and weakness. 4 The FDA label specifically warns that this can occur with excessive dosing. 4

In Healthy Volunteers

Research demonstrates that therapeutic doses of neostigmine (35 mcg/kg) in awake volunteers without neuromuscular blockade caused depolarizing neuromuscular blockade with decreased single twitch height (-14%) and significant muscle weakness. 5 A second dose further decreased single twitch height by -25%. 5

In Anesthetized Patients

In patients under anesthesia without neuromuscular blocking drugs, neostigmine 2.5 mg caused substantial reduction in peak tetanic contraction and severe tetanic fade, with slight potentiation of single twitch responses. 3 This acetylcholine-induced block could be potentiated by succinylcholine, suggesting a depolarizing component. 3

Critical Safety Considerations

The key to avoiding neostigmine-induced muscle dysfunction is proper timing and dosing based on quantitative neuromuscular monitoring: 1, 2

• Only administer neostigmine when there are at least 4 responses to TOF stimulation (corresponding to TOF ratio ≥0.2) 1, 2
• Use 40-50 mcg/kg based on ideal body weight 1, 2
• Never administer when TOF ratio is already ≥0.9 1, 2
• Always co-administer with anticholinergic agents (atropine 0.02 mg/kg or glycopyrrolate) to prevent cholinergic side effects 2, 4

Special Populations at Higher Risk

Patients with neuromuscular disorders are at unpredictable risk for adverse reactions to neostigmine, including prolonged muscle weakness and tonic responses. 6 In patients with dystrophia myotonica, neostigmine produced long-lasting muscle weakness with a train-of-four response resembling depolarizing block. 6

Post-Marketing Adverse Events

The FDA label documents fasciculations as a recognized post-marketing adverse reaction to neostigmine, along with dysarthria, muscle cramps, spasms, and weakness. 4 These cholinergic effects reflect excessive nicotinic receptor stimulation. 4

Clinical Bottom Line

Muscle twitches and fasciculations from neostigmine represent excessive cholinergic stimulation and indicate either inappropriate timing of administration (when blockade is too light or absent) or excessive dosing. 1, 4, 3 Proper quantitative neuromuscular monitoring is essential to prevent this complication. 1, 2