What is the preferred agent for reversal of neuromuscular blockade, Neostigmine (Acetylcholinesterase inhibitor) or Sugammadex (Selective relaxant binding agent)?

From the Guidelines

Sugammadex is the preferred agent for reversal of neuromuscular blockade, particularly for rocuronium and vecuronium-induced blockade, due to its faster and more complete reversal, as well as its ability to reverse deep blockade with fewer cardiovascular side effects 1.

Key Points

• Sugammadex works by directly encapsulating the neuromuscular blocking agent molecules, removing them from the neuromuscular junction, which provides faster and more complete reversal than neostigmine.
• The typical dose of sugammadex ranges from 2-16 mg/kg depending on the depth of blockade, with 2 mg/kg for moderate blockade and 4 mg/kg for deep blockade.
• Neostigmine, on the other hand, works by inhibiting acetylcholinesterase, which increases acetylcholine at the neuromuscular junction to compete with the blocking agent, but it cannot reverse deep blockade effectively and must be administered with an anticholinergic like glycopyrrolate to prevent muscarinic side effects.
• Sugammadex offers several advantages, including faster reversal time, ability to reverse deep blockade, fewer cardiovascular side effects, and no requirement for co-administration of anticholinergics.

Considerations

• Sugammadex is significantly more expensive than neostigmine and is only effective for aminosteroid neuromuscular blockers (rocuronium, vecuronium), not benzylisoquinolines like cisatracurium.
• The dose of sugammadex should be adjusted to the level of neuromuscular blockade and body weight to allow complete and rapid reversal.
• Monitoring of neuromuscular blockade is crucial to adjust the sugammadex dose and to identify potential recurrence of blockade.

Recommendations

• Sugammadex should be used as the first-line agent for reversal of neuromuscular blockade in patients undergoing surgery with rocuronium or vecuronium-induced blockade, particularly in those with deep blockade or at high risk of postoperative respiratory complications 1.
• Neostigmine may be considered as an alternative in patients with contraindications to sugammadex or in situations where sugammadex is not available.
• The choice of reversal agent should be individualized based on patient factors, such as renal function, body weight, and presence of neuromuscular disease.

From the FDA Drug Label

A multicenter, randomized, parallel-group, active-controlled, safety-assessor blinded study comparing BRIDION and neostigmine enrolled 189 patients (87 women and 102 men, 95% were ASA class 1 and 2 and 99% were Caucasian, median weights were 72 kg and 76 kg and median ages were 50 years and 51 years in the rocuronium and vecuronium groups, respectively). Patients were randomly assigned to the rocuronium or vecuronium group and underwent elective surgical procedures under general anesthesia that required endotracheal intubation and maintenance of neuromuscular blockade The surgical procedures were mainly endocrine, ocular, ENT, abdominal (gynecological, colorectal, urological), orthopedic, vascular, or dermatological. At the reappearance of T 2, after the last dose of rocuronium or vecuronium, 2 mg/kg BRIDION or 50 mcg/kg neostigmine was administered in a randomized order as a single bolus injection The time from start of administration of BRIDION or neostigmine to recovery of the TOF (T 4/T 1) ratio to 0.9 was assessed. Generally, a T 4/T 1 ratio ≥0.9 correlates with recovery from neuromuscular blockade. Return of the T 4/T 1 ratio to 0. 9 after the reappearance of T 2 was overall faster with BRIDION 2 mg/kg as compared to neostigmine 50 mcg/kg in the setting of rocuronium or vecuronium-induced neuromuscular blockade (Figures 1 and 2).

The preferred agent for reversal of neuromuscular blockade is Sugammadex, as it has been shown to be faster than Neostigmine in recovering the TOF (T 4/T 1) ratio to 0.9 in patients with rocuronium or vecuronium-induced neuromuscular blockade 2.

• Key benefits of Sugammadex include:
  • Faster recovery times
  • Effective at deeper levels of neuromuscular blockade
• Clinical decision: Sugammadex is the preferred choice for reversal of neuromuscular blockade due to its faster onset of action and effectiveness at deeper levels of blockade.

From the Research

Comparison of Neostigmine and Sugammadex

• Neostigmine is an acetylcholinesterase inhibitor, while sugammadex is a selective relaxant binding agent.
• Studies have shown that sugammadex provides faster reversal of neuromuscular blockade compared to neostigmine 3, 4, 5, 6, 7.

Efficacy of Sugammadex vs Neostigmine

• Sugammadex was found to be significantly faster in reversing vecuronium-induced neuromuscular blockade compared to neostigmine, with a geometric mean time to recovery of 2.7 minutes vs 17.9 minutes 3.
• Sugammadex also provided faster reversal of rocuronium-induced neuromuscular blockade, with a time to recovery of 1.5 minutes vs 18.6 minutes for neostigmine 4.
• A meta-analysis of randomized controlled trials found that sugammadex was superior to neostigmine in reversing neuromuscular blockade, with a faster recovery time and lower risk of adverse events 5.

Safety of Sugammadex vs Neostigmine

• Sugammadex was found to have a lower risk of adverse events compared to neostigmine, including a lower risk of bradycardia, postoperative nausea and vomiting, and postoperative residual paralysis 7.
• Sugammadex was also found to have a similar risk of serious adverse events compared to neostigmine 7.

Clinical Implications

• The use of sugammadex may be preferred over neostigmine for reversal of neuromuscular blockade due to its faster recovery time and lower risk of adverse events 3, 4, 5, 6, 7.
• However, the choice of reversal agent should be based on individual patient needs and clinical circumstances.