Can neostigmine (anticholinesterase) reverse succinylcholine (depolarizing neuromuscular blocker)-induced phase II block?

Can Neostigmine Reverse Succinylcholine Phase II Block?

Yes, neostigmine can reverse succinylcholine-induced phase II block, but only under specific conditions and with appropriate monitoring. 1, 2

Critical Prerequisites Before Reversal

Before attempting reversal of succinylcholine phase II block with neostigmine, you must confirm:

• Phase II block is actually present using peripheral nerve stimulation showing fade of responses to train-of-four stimulation 1
• At least 20 minutes of spontaneous recovery has occurred with recovery reaching a plateau, ensuring complete hydrolysis of circulating succinylcholine by plasma cholinesterase 1
• At least 4 responses to train-of-four stimulation are present at the adductor pollicis 3, 4

The most critical pitfall: If you misdiagnose the block type and give neostigmine during Phase I block (when succinylcholine is still circulating), you will paradoxically prolong the blockade rather than reverse it. 1, 5

Mechanism and Efficacy

Neostigmine works by increasing acetylcholine concentration in the synaptic cleft through reversible acetylcholinesterase inhibition. 4 For Phase II block specifically:

• Phase II block develops after prolonged succinylcholine administration (typically 2-4 mg/kg cumulative dose or infusions >90 minutes) 1, 6
• Phase II block resembles non-depolarizing blockade and responds to neostigmine reversal 2, 6
• Research demonstrates neostigmine accelerates recovery in all patients with confirmed Phase II block 2, 6

A key study showed that neostigmine successfully reversed succinylcholine Phase II block more rapidly than pancuronium-induced blockade when given 10 minutes after stopping the infusion. 2

Dosing Protocol

Standard dose: 40-50 mcg/kg of ideal body weight 3, 4

• Always administer with anticholinergic (atropine 0.02 mg/kg or glycopyrrolate) to prevent bradycardia and cardiac rhythm disturbances 4, 1
• Do not exceed 50 mcg/kg due to ceiling effect 4

Monitoring Requirements

Quantitative neuromuscular monitoring is mandatory: 3, 4

• Continue monitoring until train-of-four ratio ≥0.9 is achieved 3, 4
• Observe patient for at least 1 hour after reversal for signs of returning muscle relaxation 1
• Recovery degree correlates directly with the train-of-four ratio at time of neostigmine administration 6

Clinical Context and Timing

The transition from Phase I to Phase II block shows individual variability: 1

• Under halothane anesthesia: occurs after 2-4 mg/kg cumulative dose in all patients studied 1
• Under balanced anesthesia: more gradual transition with greater individual variability 1
• Phase I block depends on circulating succinylcholine and must clear before neostigmine becomes effective 6

Wait at least 20 minutes after stopping succinylcholine infusion before attempting reversal to ensure Phase I component has resolved. 1, 6

Contraindications and Warnings

Do not give neostigmine if: 4, 1

• Phase II block has not been confirmed with nerve stimulator
• Spontaneous recovery has not plateaued for at least 20 minutes
• TOF ratio is already ≥0.9 (neostigmine may paradoxically impair neuromuscular transmission) 3, 4

Special Populations at Risk

Patients with reduced plasma cholinesterase activity are at higher risk for prolonged Phase II block: 1

• Genetic abnormalities (homozygous atypical pseudocholinesterase: 1 in 2500 patients)
• Pregnancy, severe liver/kidney disease
• Chronic use of oral contraceptives, certain MAO inhibitors
• Organophosphate exposure

In these patients, Phase II block may develop earlier and be more prolonged, but neostigmine reversal remains effective once Phase I block has cleared. 5