What is the recommended dose of neostigmine (acetylcholinesterase inhibitor) for reversal of non-depolarizing muscle relaxants?

From the Guidelines

The recommended dose of neostigmine for reversal of non-depolarizing muscle relaxants is 0.04 mg/kg, which should be administered with an anticholinergic agent such as atropine (0.02 mg/kg). This dose is based on the most recent and highest quality study, which suggests that neostigmine should be administered when there are four responses to train-of-four (TOF) stimulation at the adductor pollicis, with a dose of 0.04 mg/kg being effective in reversing the neuromuscular blockade 1.

The use of neostigmine for reversal of non-depolarizing muscle relaxants is a common practice in anesthesia, and the dose of 0.04 mg/kg is supported by the guidelines on muscle relaxants and reversal in anesthesia 1. The administration of neostigmine with an anticholinergic agent such as atropine is also recommended to prevent the muscarinic side effects of neostigmine, such as bradycardia and increased secretions 1.

Some key points to consider when using neostigmine for reversal of non-depolarizing muscle relaxants include:

• The dose of neostigmine should be titrated based on the degree of neuromuscular blockade as measured by train-of-four monitoring 1
• Neostigmine is most effective when there is already some spontaneous recovery of neuromuscular function, and it may not adequately reverse profound neuromuscular blockade 1
• The use of neostigmine with an anticholinergic agent such as atropine can help to prevent the muscarinic side effects of neostigmine 1
• The onset of action of neostigmine begins within 1-2 minutes, with peak effect at 7-10 minutes, and a duration of action of approximately 30-60 minutes 1

From the FDA Drug Label

Doses of neostigmine methylsulfate injection should be individualized, and a peripheral nerve stimulator should be used to determine the time of initiation of neostigmine methylsulfate injection and should be used to determine the need for additional doses. A 0.03 mg/kg to 0.07 mg/kg dose of neostigmine methylsulfate injection will generally achieve a TOF twitch ratio of 90% (TOF0.9) within 10 to 20 minutes of administration. The 0.03 mg/kg dose is recommended for: i. Reversal of NMBAs with shorter half-lives, e.g., rocuronium, or ii. When the first twitch response to the TOF stimulus is substantially greater than 10% of baseline or when a second twitch is present. The 0.07 mg/kg dose is recommended for: iii. NMBAs with longer half-lives, e.g., vecuronium and pancuronium, or iv. When the first twitch response is relatively weak, i.e., not substantially greater than 10% of baseline or v. There is need for more rapid recovery.

The recommended dose of neostigmine for reversal of non-depolarizing muscle relaxants is 0.03 mg/kg to 0.07 mg/kg. The dose selection should be based on the extent of spontaneous recovery, the half-life of the NMBA being reversed, and the need for rapid reversal. Key considerations include:

• NMBA half-life: shorter half-lives (e.g., rocuronium) may require 0.03 mg/kg, while longer half-lives (e.g., vecuronium and pancuronium) may require 0.07 mg/kg.
• TOF twitch response: a response substantially greater than 10% of baseline may require 0.03 mg/kg, while a weaker response may require 0.07 mg/kg.
• Need for rapid recovery: 0.07 mg/kg may be necessary for more rapid recovery 2.

From the Research

Neostigmine Dose for Reversal

The recommended dose of neostigmine for reversal of non-depolarizing muscle relaxants is typically in the range of 0.05 to 0.07 mg/kg, often administered with glycopyrrolate to mitigate muscarinic side effects 3, 4.

Key Considerations

• Neostigmine doses of 0.05 mg/kg and 0.07 mg/kg have been compared with sugammadex for reversal of moderate and deep neuromuscular blockade, respectively 3.
• Studies suggest that neostigmine may cause muscle weakness when administered after full recovery of neuromuscular function, even at therapeutic doses 4.
• Combining neostigmine with sugammadex may reduce the required dosage of sugammadex and decrease recovery time from neuromuscular blockade 5, 6.

Comparison with Sugammadex

• Sugammadex has been shown to reverse rocuronium-induced neuromuscular blockade more rapidly than neostigmine-glycopyrrolate 7.
• The combination of half-dose sugammadex with neostigmine has been found to be non-inferior to full-dose sugammadex for reversal of deep neuromuscular blockade, offering a potential cost-saving strategy 6.

Dosage and Administration

• The specific dosage of neostigmine may vary depending on the clinical context and the depth of neuromuscular blockade 3, 5, 6.
• Neostigmine is typically administered intravenously, often in combination with an anticholinergic agent like glycopyrrolate to minimize side effects 3, 4, 7.