From the Guidelines
Neostigmine has a significant complication rate, primarily related to its cholinergic effects, with common complications including bradycardia, increased oral and bronchial secretions, nausea and vomiting, and abdominal cramps, occurring in 10-40% of patients. The most common complications of neostigmine include:
- Bradycardia (occurring in 10-20% of patients)
- Increased oral and bronchial secretions (15-30%)
- Nausea and vomiting (20-40%)
- Abdominal cramps (10-15%) More severe but less common complications include bronchospasm (1-5%) and, rarely, cardiac arrhythmias 1. These adverse effects occur because neostigmine inhibits acetylcholinesterase throughout the body, not just at the neuromuscular junction, leading to increased acetylcholine levels at muscarinic receptors. To minimize these complications, neostigmine should always be administered with an anticholinergic agent such as glycopyrrolate (0.2-0.4 mg) or atropine (0.5-1.0 mg) 1.
The typical neostigmine dose is 0.04-0.07 mg/kg (maximum 5 mg), administered only after evidence of spontaneous recovery from neuromuscular blockade (train-of-four count of at least 2 twitches) 1. Administering neostigmine too early or at too high a dose can paradoxically worsen neuromuscular blockade. Newer reversal agents like sugammadex have fewer cholinergic side effects but are more expensive and have specific indications. It is recommended to pursue quantitative monitoring of neuromuscular blockade after administration of neostigmine until a TOF ratio of 0.9 has been obtained 1.
Some studies suggest that increasing the dose of neostigmine beyond 40 mg/kg may not provide additional benefits and may even cause adverse effects on neuromuscular transmission 1. However, the best dose of neostigmine remains 40 mg/kg, and administering neostigmine at doses that are too high to reverse a very slight residual blockade is not exempt from side effects on neuromuscular transmission. The dose of neostigmine should be carefully considered, and the patient should be closely monitored for any adverse effects.
From the Research
Neostigmine Complication Rate
The complication rate of neostigmine for reversal of non-depolarizing neuromuscular blockade is a significant concern in anesthesia. Some of the complications associated with neostigmine include:
- Bradycardia
- Anaphylaxis
- Bronchospasm
- Cardiac arrest
- Atrio-ventricular (AV) block
Studies on Neostigmine Complication Rate
Several studies have investigated the complication rate of neostigmine:
- A retrospective cohort analysis 2 found that the incidence of composite outcome (bradycardia, anaphylaxis, bronchospasm, and cardiac arrest) was 3.0% in patients given neostigmine.
- A randomized, double-blinded study 3 found that neostigmine was associated with a longer time to recovery of train-of-four ratio (TOFR) ≥90% compared to sugammadex in patients with severe renal impairment.
- A case report 4 described a patient who developed type I AV block following the simultaneous administration of neostigmine and glycopyrrolate to reverse a nondepolarizing neuromuscular block.
- A systematic review 5 found that sugammadex was associated with a lower risk of adverse events, including bradycardia, postoperative nausea and vomiting, and overall signs of postoperative residual paralysis, compared to neostigmine.
- A study 6 found that the combination of sugammadex and neostigmine can reduce the dosage of sugammadex during recovery from moderate neuromuscular blockade, but may increase the incidence of systemic muscarinic side effects.
Key Findings
Some key findings from these studies include:
- Neostigmine is associated with a significant risk of complications, including bradycardia, anaphylaxis, and cardiac arrest.
- Sugammadex may be a safer alternative to neostigmine, with a lower risk of adverse events.
- The combination of sugammadex and neostigmine may be helpful in reducing the recovery time and required dosage of sugammadex, but may increase the incidence of systemic muscarinic side effects.
- Patients with severe renal impairment may be at higher risk of complications with neostigmine, and sugammadex may be a better option for these patients.