Reversal of Neuromuscular Blockade

Reversal of neuromuscular blockade restores muscle function after nondepolarising blockers to allow safe extubation and prevent residual paralysis, which causes hypoxia, aspiration, airway obstruction and postoperative pulmonary complications. Two classes are used: anticholinesterases (neostigmine, edrophonium, pyridostigmine) and the selective relaxant binding agent sugammadex.

Mechanism. Anticholinesterases inhibit acetylcholinesterase, raising acetylcholine at the junction to out-compete the blocker; the effect has a ceiling and also stimulates muscarinic receptors, so an antimuscarinic is given. Sugammadex, a modified gamma-cyclodextrin, encapsulates rocuronium (and vecuronium) in plasma, lowering free drug and drawing it from the junction.

Target. Residual block is a train-of-four ratio under 0.9. Reversal should be quantitatively monitored.

Pharmacokinetics. Neostigmine: onset 5 to 10 minutes, peak 10 minutes, duration 60 minutes, renal elimination. Sugammadex: onset 1 to 3 minutes, half-life about 2 hours, renal elimination of complex.

Neostigmine. 0.05 mg/kg intravenously (maximum 5 mg) with glycopyrronium 0.01 mg/kg or atropine 0.02 mg/kg. Give when at least two twitches are present (preferably four); no effect with a deeper block. Infants and children use the same weight-based dose.

Edrophonium. 0.5 to 1 mg/kg with atropine; faster, shorter; availability limited.

Pyridostigmine. 0.2 mg/kg with glycopyrronium; slower; rarely used for reversal.

Sugammadex dosing (actual body weight).

• 2 mg/kg when the TOF count is 2 or more.
• 4 mg/kg when the post-tetanic count is 1 to 2 with no twitches in the TOF.
• 16 mg/kg for immediate reversal 3 minutes after rocuronium 1.2 mg/kg.
• Repeat or add a further 2 to 4 mg/kg for recurrence of block.
• Does not reverse benzylisoquinoliniums or suxamethonium.

• First-line. Sugammadex for rocuronium or vecuronium where available; neostigmine with glycopyrronium for shallow block from any nondepolarising agent.
• Alternative. Neostigmine when sugammadex is unavailable, unaffordable or contraindicated; spontaneous recovery of cisatracurium or atracurium with TOF monitoring.
• Specialist. Sugammadex for cannot-intubate-cannot-oxygenate rescue after rocuronium 1.2 mg/kg (16 mg/kg).
• Emergency. Sugammadex 16 mg/kg after failed intubation with rocuronium; neostigmine for severe prolonged block when airway and ventilation are secure.

Selection. Wait for spontaneous recovery to a TOF count of 2 or more before neostigmine; confirm a TOF ratio of 0.9 or more before extubation; consider sugammadex in obesity, pulmonary disease, sleep apnoea, neuromuscular disease and rapid-turnover lists.

Contraindications.

• Neostigmine: mechanical gastrointestinal or urinary obstruction; hypersensitivity; relative in asthma, bradycardia and recent bowel anastomosis.
• Sugammadex: hypersensitivity; severe renal impairment (CrCl under 30 mL/min; not advised).

Serious adverse effects.

• Neostigmine: bradycardia and asystole, bronchospasm, salivation, nausea and vomiting, abdominal cramps; paradoxical weakness with excess or full block.
• Sugammadex: anaphylaxis, bradycardia and asystole, cough, recurrent block if underdosed, prolonged activated partial thromboplastin time and prothrombin time.

Major interactions.

• Sugammadex binds hormonal contraceptives: counts as a missed pill dose (extra contraception for 7 days).
• Toremifene and fusidic acid displace rocuronium from sugammadex.
• Aminoglycosides, magnesium and hypothermia prolong block and may defeat neostigmine.
• Beta-blockers with neostigmine: bradycardia.

Common prescribing errors.

• Neostigmine at TOF count of 0 or 1.
• Omitting antimuscarinic.
• Sugammadex dosed by ideal body weight when the actual weight dose is intended.
• Assuming sugammadex reverses atracurium.
• No quantitative monitoring.

Special groups.

• Pregnancy: neostigmine used at caesarean section with glycopyrronium; sugammadex has limited data.
• Breastfeeding: limited data; transfer into milk is expected to be small.
• Children: neostigmine 0.05 mg/kg; sugammadex 2 to 4 mg/kg in older children.
• Older adults: slower recovery; use sugammadex when possible.
• Kidney: sugammadex avoided at CrCl under 30 mL/min; neostigmine clearance reduced.
• Liver: no adjustment.
• East Africa: sugammadex may be unavailable or costly; use a nerve stimulator where possible, and delay extubation until clinical criteria are fully met.

Monitoring. Train-of-four ratio before extubation; ECG for bradycardia for 10 minutes after reversal; respiratory rate, tidal volume, sustained head lift, oxygen saturation in recovery; observe for recurrent block for at least 30 minutes.

Referral and escalation. Anaphylaxis, asystole, residual paralysis in recovery (re-sedate, ventilate and re-reverse), failed reversal with suspected cholinesterase deficiency or neuromuscular disease.

Comparison with alternative classes. Sugammadex reverses even profound rocuronium block quickly and predictably, but costs more, has limited renal use and does not work on benzylisoquinoliniums; neostigmine is cheap but ceiling-limited, slower and cholinergic.