Neostigmine in Healthy Individuals: Muscle Effects
Yes, a healthy person taking 45mg of neostigmine would likely experience muscle twitching and fasciculations, along with potentially dangerous muscle weakness and respiratory impairment.
Understanding the Dose Context
The question asks about "45mg" which I interpret as 45 mcg/kg (the standard dosing unit for neostigmine), as an absolute 45mg dose would be lethal. For a 70kg person, this equals approximately 3.15mg total dose. 1, 2
Why Muscle Twitching Occurs
Neostigmine causes muscle fasciculations through excessive acetylcholine accumulation at nicotinic receptors. 2 As an acetylcholinesterase inhibitor, it prevents breakdown of acetylcholine in the synaptic cleft, leading to overstimulation of muscle receptors. 2, 3
The Critical Problem: Administration Without Neuromuscular Blockade
Giving neostigmine to a healthy person (without neuromuscular blockade) is dangerous and contraindicated. 1, 2 Here's what happens:
Paradoxical Muscle Weakness
- When administered at TOF ratio ≥0.9 (normal neuromuscular function), neostigmine paradoxically impairs neuromuscular transmission rather than improving it 2, 3
- A 40 mcg/kg dose given when TOF >0.9 can decrease the TOF ratio and cause muscle weakness lasting 17-52 minutes 2
Documented Effects in Healthy Volunteers
A high-quality 2018 study demonstrated that therapeutic doses of neostigmine (35 mcg/kg) in healthy volunteers without neuromuscular blockade caused: 4
- Grip strength reduction of 20% at 5 minutes 4
- Depolarizing neuromuscular blockade with 14% decrease in single twitch height 4
- Restrictive respiratory pattern with 15% decrease in FEV1 and 20% decrease in FVC 4
- A second dose (total ~70 mcg/kg) worsened effects: 41% grip strength reduction, 25% single twitch decrease 4
Respiratory Complications
- Upper airway obstruction risk: Neostigmine at 30 mcg/kg given at TOF ratio 1.0 significantly increased upper airway closing pressure and reduced genioglossus muscle activity 1
- Decreased airway patency and laryngeal dilation capacity 1
- High-dose neostigmine (>60 mcg/kg) increases odds of postoperative respiratory complications 8-fold 5
Clinical Manifestations at 45 mcg/kg
At this dose in a healthy person, expect: 4
- Visible muscle fasciculations and twitching from nicotinic receptor overstimulation 2
- Progressive muscle weakness affecting grip strength and respiratory muscles 4
- Respiratory distress with restrictive breathing pattern 4, 6
- Muscarinic side effects: abdominal cramping, nausea, bradycardia, bronchial constriction, blurred vision 6, 7
Critical Safety Point
Neostigmine should NEVER be administered to individuals without residual neuromuscular blockade. 1, 2 The Anaesthesia society strongly recommends:
- Only administer when TOF shows at least 4 responses (TOF ratio ≥0.2) 1, 2, 3
- Never give when TOF ratio is already ≥0.9 2, 3
- Always co-administer with anticholinergic agents (atropine 0.02 mg/kg or glycopyrrolate) 2, 3, 8
Bottom Line
A 45 mcg/kg dose in a healthy person would cause muscle twitching/fasciculations initially, followed by paradoxical muscle weakness, respiratory impairment, and potentially life-threatening complications. 2, 4 This represents dangerous misuse of the medication outside its intended indication for reversing non-depolarizing neuromuscular blockade. 8