What is the use of neostigmine (an acetylcholinesterase inhibitor)?

From the Guidelines

Neostigmine should be administered after awaiting spontaneous reversal equal to four muscle responses at the adductor pollicis following TOF stimulation of the ulnar nerve to ensure safe and effective reversal of neuromuscular blockade. This recommendation is based on the strongest and most recent evidence from the study published in 2020 1, which suggests that the degree of blockade prior to reversal by neostigmine must have spontaneously recovered at least four visual or tactile TOF responses.

Key Considerations for Neostigmine Administration

• The dose of neostigmine is typically 0.03-0.07 mg/kg, administered intravenously, and always with an anticholinergic agent like glycopyrrolate (0.01 mg/kg) or atropine (0.01-0.02 mg/kg) to prevent bradycardia and other muscarinic side effects.
• Neostigmine works by inhibiting acetylcholinesterase, which increases acetylcholine levels at neuromuscular junctions, enhancing muscle contraction.
• When administering neostigmine, monitor for cholinergic side effects including bradycardia, bronchospasm, increased secretions, nausea, vomiting, and abdominal cramps.
• The medication should be used cautiously in patients with asthma, bradycardia, recent myocardial infarction, epilepsy, or intestinal obstruction.

Monitoring and Reversal of Neuromuscular Blockade

• Ensure adequate neuromuscular monitoring when using neostigmine for reversal of neuromuscular blockade to confirm complete reversal before extubation, as recommended by recent guidelines 1.
• Quantitative monitoring of neuromuscular blockade after administration of neostigmine until a TOF ratio of 0.9 has been obtained is recommended 1.
• Selective relaxant binding agents (SRBA) such as sugammadex may be considered as an alternative to neostigmine for reversal of neuromuscular blockade, as they have been shown to more predictably reverse NMB and reduce the risk of bulbar dysfunction and aspiration 1.

Important Safety Considerations

• Always prioritize the patient's safety and take necessary precautions to prevent complications, such as aspiration and postoperative pulmonary complications, especially in high-risk patients undergoing emergency laparotomy 1.
• Ensure that the patient has achieved a TOF ratio of more than 0.9 before extubation to confirm complete reversal of neuromuscular blockade.

From the FDA Drug Label

Neostigmine methylsulfate injection, a cholinesterase inhibitor, is indicated for the reversal of the effects of non-depolarizing neuromuscular blocking agents (NMBAs) after surgery The primary use of neostigmine is for the reversal of non-depolarizing neuromuscular blocking agents after surgery 2. Key points about neostigmine use include:

• It is a competitive cholinesterase inhibitor that increases acetylcholine levels in the synaptic cleft, competing with non-depolarizing neuromuscular blocking agents to reverse neuromuscular blockade 2
• Neostigmine does not readily cross the blood-brain barrier, and therefore does not significantly affect cholinergic function in the central nervous system 2, 2

From the Research

Use of Neostigmine

• Neostigmine is used for the reversal of non-depolarizing neuromuscular blockade in adults, but it has significant limitations, such as indirect mechanisms of reversal, limited and unpredictable efficacy, and undesirable autonomic responses 3.
• Studies have shown that sugammadex is more effective and safer than neostigmine in reversing neuromuscular blockade, with faster recovery times and fewer adverse events 3.
• Neostigmine can cause muscle weakness and depolarizing neuromuscular blockade in healthy volunteers, even at therapeutic doses 4.
• The neostigmine test is used to diagnose myasthenia gravis, and it has been shown to be effective in improving clinical symptoms and neurophysiological recordings in patients with the disease 5, 6.
• A systematic review and meta-analysis found that neostigmine is effective and safe for neuromuscular blockade reversal in patients under general anesthesia, reducing the length of stay in the post-anesthesia care unit and the time to recovery of train-of-four ratio ≥0.9 7.

Efficacy and Safety of Neostigmine

• Neostigmine has been shown to be effective in reversing neuromuscular blockade, but its efficacy can be limited by its indirect mechanism of action and unpredictable response 3.
• Sugammadex has been shown to be more effective than neostigmine in reversing neuromuscular blockade, with faster recovery times and fewer adverse events 3.
• Neostigmine can cause adverse events, such as bradycardia, postoperative nausea and vomiting, and residual paralysis, but the risk of these events can be reduced with the use of sugammadex 3.
• A systematic review and meta-analysis found that neostigmine is safe for neuromuscular blockade reversal in patients under general anesthesia, with no difference in adverse events compared to the control group 7.

Clinical Applications of Neostigmine

• Neostigmine is used to diagnose myasthenia gravis, and it has been shown to be effective in improving clinical symptoms and neurophysiological recordings in patients with the disease 5, 6.
• Neostigmine is used for the reversal of non-depolarizing neuromuscular blockade in adults, and it has been shown to be effective in reducing the length of stay in the post-anesthesia care unit and the time to recovery of train-of-four ratio ≥0.9 7.
• Neostigmine can be used to improve muscle strength and respiratory function in patients with myasthenia gravis, but its use can be limited by its potential to cause muscle weakness and depolarizing neuromuscular blockade 4, 5.