The effects of acetylcholinesterase inhibitors on morbidity after general anesthesia and surgery. (15th August 2020)

• Record Type: Journal Article
• Authors: Shaydenfish, Denys; Wongtangman, Karuna; Eikermann, Matthias; Schaefer, Maximilian S.
• Is Part Of: Neuropharmacology. Volume 173(2020)
• Publication Date: 2020-08-15
• Subjects: Reversal agents -- Neuromuscular blockade -- Acetylcholine -- Muscarine -- Nicotine -- Side-effects -- Respiratory -- Cardiovascular -- Mortality; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2020.108134
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Non-depolarizing neuromuscular blocking agents are used during general anesthesia to facilitate intubation and optimize surgical conditions. When patients leave the operating room after surgery, postoperative residual neuromuscular block occurs frequently, increasing vulnerability to respiratory complications such as hypoxemia and unplanned postoperative mechanical ventilation. To restore neuromuscular transmission and skeletal muscle strength, anesthesiologists typically administer peripherally acting acetylcholinesterase inhibitors such as neostigmine. However, neostigmine's desirable effects have a narrow therapeutic range. Even at recommended dose (15–50 μg/kg), neostigmine induces nicotinic (upper airway muscle weakness leading to dysphagia and upper airway obstruction, and decreased maximum inspiratory airflow) and muscarinic (blurred vision, bronchial constriction, abdominal cramping and nausea) side effects. Recent data have questioned as to whether neostigmine reversal of neuromuscular blockade improves relevant patient outcomes such as postoperative respiratory and perioperative cardiovascular complications. A central strategy to avoid side effects of neuromuscular blocking agents is their judicious use based on quantitative monitoring of neuromuscular transmission using repetitive peripheral nerve stimulation (train-of-four ratio). Peripherally acting acetylcholinesterase inhibitors such as neostigmine should then only be administered when indicated and dosed based on results of the train-of-four ratio. Graphical abstract: Image 1 Highlights: Neostigmine is the most commonly used acetylcholinesterase inhibitor in perioperative medicine. Neostigmine reverses residual effects of non-depolarizing neuromuscular blocking agents. Neostigmine reversal has a narrow therapeutic range due to ceiling and nicotinic and muscarinic side effects. It is uncertain whether neostigmine reversal improves relevant postoperative patient outcomes. Administration of neostigmine should be based on quantitative neuromuscular monitoring.