Can Neostigmine (acetylcholinesterase inhibitor) and Glycopyrolate (anticholinergic) be used together?

Neostigmine and Glycopyrrolate: Safe and Effective Combination for Neuromuscular Blockade Reversal

Neostigmine and glycopyrrolate should be administered together for neuromuscular blockade reversal, with glycopyrrolate given prior to or simultaneously with neostigmine to prevent unwanted cholinergic side effects. 1, 2

Mechanism and Rationale

Neostigmine is an acetylcholinesterase inhibitor that increases acetylcholine concentration at the neuromuscular junction to reverse non-depolarizing muscle relaxants. However, this increased acetylcholine also affects muscarinic receptors throughout the body, potentially causing:

• Bradycardia and cardiac arrhythmias
• Increased bronchial secretions
• Bronchoconstriction
• Increased gastrointestinal motility

Glycopyrrolate, an anticholinergic agent, selectively blocks these muscarinic effects while minimally affecting the nicotinic receptors at the neuromuscular junction, allowing neostigmine to effectively reverse neuromuscular blockade without unwanted side effects 3, 4.

Proper Administration

Dosing

• Glycopyrrolate: 0.2 mg for each 1.0 mg of neostigmine 2
• Neostigmine: 0.03-0.07 mg/kg (maximum 5 mg) 1

Administration Method

• Both medications should be administered intravenously
• Can be mixed in the same syringe and administered simultaneously 2
• Alternatively, glycopyrrolate can be given prior to neostigmine, especially in the presence of bradycardia 1
• Administer slowly over at least 1 minute 1

Monitoring Requirements

• Train-of-four (TOF) monitoring is essential before administering neostigmine 3, 1
• There must be at least a 10% twitch response to the first stimulus in TOF before administration 1
• Continue TOF monitoring after administration until TOF ratio reaches ≥0.9 3
• Optimal administration is when four responses to TOF are present (TOF ratio ≥0.2) 3

Special Considerations

Depth of Blockade

• For very slight residual blockade (TOF ratio >0.5), consider reducing neostigmine dose by half 3
• Do not administer neostigmine when TOF ratio is already 1.0, as it may impair neuromuscular transmission and reduce upper airway patency 3

Anesthetic Agent Influence

• Recovery times are significantly shorter with propofol anesthesia compared to sevoflurane 3
• Under propofol anesthesia, complete reversal typically occurs within 10 minutes
• Under sevoflurane anesthesia, complete reversal may take longer 3

Potential Complications

1. Cardiovascular Effects:

   • Inadequate glycopyrrolate dosing may result in bradycardia or AV block 5
   • Excessive glycopyrrolate may cause tachycardia

2. Respiratory Effects:

   • Administering neostigmine when TOF ratio is already 1.0 may decrease upper airway patency and reduce laryngeal dilation capacity 3

3. Recurarization:

   • Inadequate monitoring after reversal may miss recurarization
   • Continue monitoring until TOF ratio ≥0.9 is maintained 3, 6

Clinical Pearls

• The 10 μg/kg dose of glycopyrrolate with neostigmine provides the most stable heart rates 7
• In patients with certain conditions (e.g., those on antiepileptic drugs), there may be increased risk of AV block with neostigmine-glycopyrrolate combination 5
• The combination has been shown to be effective for other uses, such as bowel evacuation in spinal cord injury patients 8
• Alternative combinations (e.g., atropine 0.6 mg with glycopyrrolate 0.2 mg) can also effectively counteract neostigmine's muscarinic effects 9

Conclusion

The combination of neostigmine and glycopyrrolate is safe and effective for neuromuscular blockade reversal when properly administered and monitored. The key is appropriate dosing, timing, and continuous monitoring to ensure complete reversal while minimizing side effects.