What is the correlation between the train of four (TOF) and the time of reversibility for neuromuscular blockade?

From the Guidelines

The timing of neuromuscular blockade reversal is critical for patient safety during anesthesia recovery, and the train of time of reversability for neuromuscular blockade should be guided by the depth of blockade and the choice of reversal agent, with sugammadex providing faster and more reliable reversal than neostigmine, especially for deep blocks 1.

Key Considerations

• For traditional reversal agents like neostigmine, administration should occur when there is evidence of spontaneous recovery, typically when train-of-four (TOF) count shows at least 2-4 twitches present 1.
• Neostigmine (0.04-0.07 mg/kg) with an anticholinergic like glycopyrrolate (0.01 mg/kg) should be given, with full reversal expected within 10-15 minutes 1.
• For sugammadex, dosing depends on blockade depth: 2 mg/kg for moderate block (TOF count ≥2), 4 mg/kg for deep block (1-2 post-tetanic counts), and 16 mg/kg for immediate reversal after rocuronium 1.

Monitoring and Reversal

• Quantitative monitoring with TOF ratio measurement is superior to qualitative assessment, with a TOF ratio ≥0.9 indicating adequate reversal 1.
• Premature reversal attempts with neostigmine when deep blockade is present may result in inadequate reversal and increased risk of residual paralysis, while delayed reversal extends recovery time unnecessarily 1.
• Monitoring should continue until full recovery is confirmed to prevent complications like hypoxemia, aspiration, and respiratory failure 1.

Reversal Agents

• Sugammadex provides faster and more reliable reversal than neostigmine, especially for deep blocks 1.
• The dose of sugammadex required for reversal was determined for four degrees of blockade, with higher doses required for deeper blocks 1.

From the FDA Drug Label

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. 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 Return of the T 4/T 1 ratio to 0. 9 in patients with 1 to 2 PTCs with BRIDION 4 mg/kg had a wider range of recovery times but the median time to recovery was comparable to the study of reversal at T 2 (2.7 minutes with 25 th and 75 th percentiles of 2.1 and 4.3 minutes for rocuronium [N=37], and 3.3 minutes with 25 th and 75 th percentiles of 2.3 and 6. 6 minutes for vecuronium [N=47])

The time to recovery from neuromuscular blockade is as follows:

• For rocuronium with BRIDION 2 mg/kg: faster recovery compared to neostigmine
• For vecuronium with BRIDION 2 mg/kg: faster recovery compared to neostigmine
• For rocuronium with BRIDION 4 mg/kg at 1 to 2 PTCs: median time to recovery of 2.7 minutes
• For vecuronium with BRIDION 4 mg/kg at 1 to 2 PTCs: median time to recovery of 3.3 minutes 2

From the Research

Correlation Between Train of Time and Reversability of Neuromuscular Blockade

• The time to achieve train-of-four (TOF) ratios of 0.7 and 0.9 was significantly shorter with sugammadex compared to edrophonium or neostigmine 3.
• Sugammadex, 4 mg/kg IV, more rapidly and effectively reversed residual neuromuscular blockade when compared with neostigmine (70 microg/kg IV) and edrophonium (1 mg/kg IV) 3.
• The incidence of residual neuromuscular block (rNMB) at 2 min after sugammadex administration was 19.2% and declined to 2.8% at 6 min post administration, whereas rNMB incidence at 2 min after neostigmine administration was 100% and was 82% at 6 min post administration 4.

Factors Affecting Reversal of Neuromuscular Blockade

• The combination of rocuronium or vecuronium plus sugammadex is more effective and more rapid in reversing NMB compared with combinations of rocuronium, vecuronium, cisatracurium, or pancuronium plus neostigmine 4.
• Sugammadex administered at recommended doses provides rapid and predictable reversal of rocuronium and vecuronium-induced moderate and deep NMB 5.
• Modest increases in mean recovery time were associated with vecuronium use, mild-to-moderate renal impairment, and geographic location 5.

Comparison of Sugammadex and Neostigmine

• Sugammadex was associated with less frequent dry mouth than neostigmine 3.
• There was no difference between sugammadex and neostigmine with glycopyrrolate in regard to hemodynamic instability that required escalation of treatment within 30 minutes after receiving either agent for the reversal of rocuronium 6.
• Sugammadex administered 3 min after rocuronium 1.2 mg/kg resulted in rapid recovery (1.7 min) 5.