"The neuromuscular blocking drugs paralyse but do not anaesthetise. The two commandments follow from that single fact: never paralyse a patient you cannot ventilate, and never let one wake before the block is fully reversed."
Synthesised from Miller's Anesthesia; Morgan & Mikhail's Clinical Anesthesiology; Stoelting's Pharmacology & Physiology in Anesthetic Practice.How a nerve impulse becomes a muscle twitch
Every blocker acts on the nicotinic acetylcholine receptor at the motor end-plate. Understanding the normal cycle makes the pharmacology obvious.
Synthesis & storage
Acetylcholine (ACh) is made from acetyl-CoA + choline by choline acetyltransferase and stored in vesicles at the nerve terminal.
Release
The action potential opens voltage-gated Caยฒโบ channels; Caยฒโบ influx triggers vesicle fusion and ACh release into the cleft.
Receptor activation
ACh binds both ฮฑ-subunits of the postjunctional nicotinic receptor โ cation channel opens โ end-plate depolarisation โ muscle action potential โ contraction.
Termination
Acetylcholinesterase in the cleft hydrolyses ACh within milliseconds; choline is recycled. The end-plate repolarises, ready for the next impulse.
The pharmacological levers: non-depolarisers compete at the receptor (block step 3); suxamethonium over-stimulates it; anticholinesterases (neostigmine) raise ACh by blocking step 4; sugammadex removes the drug from the plasma entirely.
Two mechanisms, two chemical families
| Class | Mechanism | Examples |
|---|---|---|
| Depolarising | Receptor agonist โ sustained depolarisation โ fasciculation then flaccid paralysis | Suxamethonium (succinylcholine) |
| Non-depolarising โ aminosteroid | Competitive antagonist at the receptor | Rocuronium, Vecuronium, Pancuronium |
| Non-depolarising โ benzylisoquinolinium | Competitive antagonist; organ-independent breakdown | Atracurium, Cisatracurium, Mivacurium |
Aminosteroids ("-onium/-uronium") are reversed by sugammadex and depend on hepatic/renal clearance. Benzylisoquinoliniums are not reversed by sugammadex but atracurium/cisatracurium clear by organ-independent Hofmann elimination โ the drugs of choice in renal and hepatic failure.
Fast on, fast off โ and a long list of hazards
Dose 1โ1.5 mg/kg IV; onset ~45โ60 s, duration ~5โ10 min. Its speed makes it the classic rapid-sequence induction relaxant. It is hydrolysed by plasma (pseudo)cholinesterase.
Complications to know cold
Exaggerated Kโบ efflux via up-regulated extrajunctional receptors โ avoid after ~24โ72 h in burns, denervation/spinal cord injury, prolonged immobility and severe sepsis.
Suxamethonium is a trigger (with volatiles). Masseter spasm may be the first sign.
Prolonged paralysis in pseudocholinesterase deficiency โ quantified by the dibucaine number (normal ~80; homozygous atypical ~20). Management: ventilate & sedate until spontaneous recovery.
Bradycardia (esp. second dose / children โ pre-treat atropine), myalgia, raised intracranial, intraocular & intragastric pressure, transient hyperkalaemia even in normals (~0.5 mmol/L).
Choosing between the competitive blockers
| Agent | Intubating dose | Onset | Duration | Elimination / notes |
|---|---|---|---|---|
| Rocuronium | 0.6 mg/kg (1.2 for RSI) | ~60โ90 s | ~30โ40 min | Hepatic; sugammadex-reversible โ the non-depolarising RSI alternative to suxamethonium |
| Vecuronium | 0.1 mg/kg | ~2โ3 min | ~30โ40 min | Hepatic/renal; sugammadex-reversible; cardiostable |
| Atracurium | 0.5 mg/kg | ~2โ3 min | ~30 min | Hofmann elimination (organ-independent); histamine release; metabolite laudanosine |
| Cisatracurium | 0.15 mg/kg | ~3โ5 min | ~35โ45 min | Hofmann elimination; no histamine release; ideal in renal/hepatic failure & ICU |
| Pancuronium | 0.1 mg/kg | ~3โ5 min | ~60โ90 min (long) | Renal; vagolytic โ tachycardia; largely historical |
Fast & reversible: rocuronium + sugammadex now rivals suxamethonium for RSI where suxamethonium is contraindicated. Organ-independent: cisatracurium for the patient in renal/hepatic failure or long ICU infusions.
You cannot manage what you do not measure
A peripheral nerve stimulator (e.g. ulnar nerve โ adductor pollicis) delivers four supramaximal twitches (2 Hz). Interpretation depends on the number of twitches and the presence of fade.
| Pattern | Meaning |
|---|---|
| TOF count 0 (+ post-tetanic count) | Deep/profound block โ use PTC to gauge depth |
| 1โ3 twitches | Moderate block โ neostigmine reversal possible once โฅ2 twitches |
| Fade (T4 < T1) | Non-depolarising (or Phase II) block โ the hallmark |
| No fade | Normal, or a depolarising Phase I block |
| TOF ratio โฅ 0.9 | Adequate recovery โ the threshold for safe extubation |
A TOF ratio 0.7โ0.9 still impairs pharyngeal function and the hypoxic ventilatory response โ clinical tests (5-s head lift) miss it. Confirm โฅ0.9 with quantitative monitoring before extubation.
Two very different tools
Neostigmine (+ glycopyrrolate)
Inhibits acetylcholinesterase โ more ACh to out-compete the blocker. Only works once recovery has begun (โฅ2 twitches / TOF count โฅ2) โ it has a ceiling. Give an antimuscarinic (glycopyrrolate/atropine) to block bradycardia, salivation and bronchospasm.
Sugammadex
A modified ฮณ-cyclodextrin that encapsulates rocuronium/vecuronium in plasma โ reverses even profound block. Dose 2 mg/kg (moderate, โฅ2 twitches), 4 mg/kg (deep, PTC 1โ2), 16 mg/kg (immediate reversal after an intubating dose). Does not reverse benzylisoquinoliniums.
Caveats for sugammadex: binds hormonal contraceptives (advise extra contraception for 7 days), rare anaphylaxis, and needs a higher re-dose if rocuronium is given again soon.
When the choice of relaxant changes
| Situation | Approach |
|---|---|
| Renal / hepatic failure | Cisatracurium / atracurium (Hofmann elimination, organ-independent) |
| Rapid-sequence induction | Suxamethonium 1โ1.5 mg/kg, or rocuronium 1.2 mg/kg (with sugammadex available) |
| Malignant hyperthermia risk | Avoid suxamethonium; all non-depolarisers are safe |
| Myasthenia gravis | Resistant to suxamethonium, very sensitive to non-depolarisers โ titrate tiny doses with monitoring |
| Pseudocholinesterase deficiency | Prolonged suxamethonium/mivacurium block โ ventilate until recovery; dibucaine number confirms |
| Critical illness / prolonged immobility | Avoid suxamethonium (hyperkalaemia); watch for ICU-acquired weakness with prolonged NMB use |
Where it goes wrong
- Paralysing before confirming you can ventilate/oxygenate.
- Giving suxamethonium to a burn/denervation/SCI patient beyond the safe window โ hyperkalaemic arrest.
- Reversing with neostigmine at TOF count 0 โ it cannot work with no twitches (use sugammadex or wait).
- Extubating on clinical signs alone instead of a quantitative TOF ratio โฅ0.9.
- Forgetting the antimuscarinic with neostigmine โ bradycardia/secretions.
- Expecting sugammadex to reverse atracurium/cisatracurium (it won't).
High-yield one-liners
Q: Dibucaine number in homozygous atypical pseudocholinesterase?
~20 (normal ~80) โ prolonged suxamethonium apnoea.
Q: Which relaxants are organ-independent?
Atracurium & cisatracurium โ Hofmann elimination; drugs of choice in renal/hepatic failure.
Q: TOF ratio for safe extubation?
โฅ0.9 (quantitative).
Q: Sugammadex doses?
2 mg/kg (moderate), 4 mg/kg (deep), 16 mg/kg (immediate reversal).
Q: Muscle relaxants in myasthenia gravis?
Resistant to suxamethonium; markedly sensitive to non-depolarisers.
Q: Metabolite of atracurium that can cause CNS excitation?
Laudanosine.
Side-by-side comparisons
Depolarising (suxamethonium) vs Non-depolarising block
| Feature | Depolarising | Non-depolarising |
|---|---|---|
| Mechanism | Receptor agonist | Competitive antagonist |
| Fasciculations | Yes (before paralysis) | No |
| Fade on TOF / tetanus | Absent (Phase I) | Present |
| Post-tetanic potentiation | Absent | Present |
| Effect of neostigmine | Augments block | Reverses block |
Neostigmine vs Sugammadex
| Feature | Neostigmine | Sugammadex |
|---|---|---|
| Mechanism | Anticholinesterase (โ ACh) | Encapsulates the drug |
| Works at deep block? | No โ needs โฅ2 twitches | Yes โ even profound block |
| Reverses which agents? | All non-depolarisers (partially) | Only aminosteroids (roc/vec) |
| Co-drug | Antimuscarinic needed | None |
| Notable caveat | Bradycardia, ceiling effect | Binds contraceptives; costly |
Aminosteroid vs Benzylisoquinolinium
| Feature | Aminosteroid | Benzylisoquinolinium |
|---|---|---|
| Examples | Rocuronium, vecuronium, pancuronium | Atracurium, cisatracurium, mivacurium |
| Histamine release | No | Atracurium yes; cisatracurium no |
| Elimination | Hepatic/renal | Hofmann (organ-independent) |
| Sugammadex-reversible | Yes | No |
References
- Gropper MA, Cohen NH, Eriksson LI, et al. (eds). Miller's Anesthesia. 9th ed. Elsevier; 2020.
- Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail's Clinical Anesthesiology. 7th ed. McGraw-Hill; 2022.
- Flood P, Rathmell JP, Urman RD. Stoelting's Pharmacology & Physiology in Anesthetic Practice. 6th ed. Wolters Kluwer; 2022.
- Naguib M, Brull SJ, Kopman AF, et al. Consensus Statement on Perioperative Use of Neuromuscular Monitoring. Anesth Analg. 2018;127(1):71โ80.