Muscle Groups Involved in Neostigmine Overdose
Neostigmine overdose causes widespread muscarinic and nicotinic effects affecting smooth muscle, cardiac muscle, respiratory muscles (including the diaphragm and intercostals), upper airway muscles (particularly the genioglossus), and skeletal muscles throughout the body, leading to a cholinergic crisis characterized by paradoxical muscle weakness despite increased acetylcholine. 1
Primary Muscle Groups Affected
Smooth Muscle Systems
- Gastrointestinal smooth muscle becomes hyperactive, producing nausea, vomiting, and diarrhea as classic muscarinic symptoms of overdose 1
- Bronchial smooth muscle contracts excessively, leading to increased bronchial secretions and potential bronchospasm 1
Cardiac Muscle
- Myocardium experiences direct muscarinic effects causing bradycardia, which is a hallmark sign of neostigmine toxicity 1
Respiratory Muscle Complex
- Diaphragm and intercostal muscles become progressively weaker despite the cholinergic stimulation, creating a life-threatening situation where respiratory muscle involvement can result in death 1
- Therapeutic doses of neostigmine (35 μg/kg) decrease forced vital capacity by 20% and forced expiratory volume by 15%, demonstrating significant respiratory muscle impairment 2
- Upper airway muscles, specifically the genioglossus, show markedly reduced activity in response to negative pharyngeal pressure (decreased by 37%), increasing upper airway collapsibility and critical closing pressure by 27-38% 3
Skeletal Muscle - Generalized Involvement
- All voluntary skeletal muscle groups are affected by the depolarizing neuromuscular blockade that occurs with overdose, manifesting as increasing muscle weakness throughout the body 1, 2
- Hand grip strength decreases by 20% with a single therapeutic dose and by 41% with a second dose, demonstrating dose-dependent skeletal muscle weakness 2
- Fasciculations occur profusely in multiple muscle groups (average 6-7 muscle groups with standard dosing), representing repetitive nerve terminal discharges 4
Mechanism of Muscle Involvement
The paradoxical muscle weakness occurs through depolarizing neuromuscular blockade despite increased acetylcholine at the neuromuscular junction 2. This creates a critical clinical scenario where:
- Single twitch height decreases by 14% with one dose and 25% with repeated dosing, while train-of-four ratio may remain unchanged, making detection difficult 2
- The excessive acetylcholine causes sustained depolarization at the motor endplate, preventing normal repolarization and subsequent muscle contraction 2
Clinical Pitfall to Avoid
The most dangerous aspect is that cholinergic crisis from overdose can be extremely difficult to distinguish from myasthenic crisis on a symptomatic basis, as both present with extreme muscle weakness 1. However, the treatment is radically different:
- Cholinergic crisis requires immediate withdrawal of all anticholinesterase drugs and prompt atropine administration 1
- Myasthenic crisis requires more intensive anticholinesterase therapy 1
- Edrophonium chloride testing and clinical judgment are essential for differentiation, as giving more neostigmine during cholinergic crisis could have grave consequences 1