Neuromuscular blockers,
as they have actually been examined.

Because it is the less potent drug. Potency is expressed as ED95 — rocuronium 0.3 mg/kg against vecuronium 0.05 — so achieving the same receptor occupancy needs about six times as many rocuronium molecules. The larger number of molecules in plasma creates a steeper concentration gradient from plasma to the neuromuscular junction, and the junctional concentration rises faster. Onset time is inversely related to potency across the whole class.

It is worth adding that these drugs are perfusion-limited rather than diffusion-limited. They are permanently charged and do not cross membranes, so what governs arrival is blood flow to the muscle, not diffusion. That is why cardiac output and muscle blood flow are the other determinants, and why a low cardiac output state slows onset.

Likely follow-ups

• What else would speed the onset of rocuronium in a given patient?
• Would you expect onset to be faster or slower in an elderly patient, and why?
• How would you make cisatracurium act faster, and what would it cost you?

Neuromuscular Blockers 1: Classification and Structure →

My first step is to confirm that this is neuromuscular in origin — I would exclude residual anaesthetic, opioid and hypocapnia — and then attach a nerve stimulator, because the pattern tells me what kind of block I am dealing with and whether it is still phase I.

The cause is prolonged block from reduced plasma cholinesterase activity, and I would divide the causes into genetic and acquired. Genetic: the atypical, silent and fluoride-resistant alleles, with the homozygous atypical genotype giving a block of four to eight hours and a heterozygote giving something much shorter. Acquired: pregnancy, liver disease, renal failure, cardiac failure, thyrotoxicosis, malignancy, and drugs — metoclopramide, ketamine, the oral contraceptive pill, lithium, ester local anaesthetics, cytotoxics, and neostigmine itself.

Management is supportive: maintain sedation and ventilation until the block resolves, monitoring recovery with a stimulator. The important negative is that I would not give an anticholinesterase to a phase I block, since it would augment it. Afterwards the patient needs enzyme activity and phenotyping, family screening, and a warning card — and mivacurium avoided as well, since the same enzyme metabolises it.

Likely follow-ups

• What would a dibucaine number of 20 tell you, and what would it not tell you?
• How would you manage this patient now?
• Which other drug used in anaesthesia would you avoid in this patient in future?

Neuromuscular Blockers 2: Suxamethonium →

For a healthy elderly patient having an intermediate-length case I would use either rocuronium or atracurium, and I would choose on organ function rather than on age alone. Rocuronium is convenient — fast onset, and reversible with sugammadex at any depth — but it is cleared by liver and kidney, both of which decline with age, so the duration is prolonged and less predictable.

The dose in mg/kg is unchanged. What changes is the interval: I would give the normal intubating dose, expect a slower onset because cardiac output and circulation time are lower and these drugs are perfusion-limited, and then top up against a train-of-four rather than against the clock, because the duration of each dose is longer and less predictable.

With a creatinine clearance of 20 I would move to atracurium or cisatracurium. Hofmann elimination and non-specific ester hydrolysis are organ-independent, so neither renal nor hepatic impairment prolongs them. Laudanosine does accumulate in renal failure, but that is a consideration for prolonged infusion in intensive care rather than for a single theatre case.

Likely follow-ups

• What would change your answer if her creatinine clearance were 20 mL/min?
• How would you dose it, and how would you know when to give more?
• Would you expect onset to be faster or slower than in a 30-year-old, and why?

Neuromuscular Blockers 3: The Non-Depolarising Agents →

A train-of-four count of zero tells me the block is deep — essentially complete receptor occupancy — but it cannot tell me how deep, because the pattern has already bottomed out. So my next step is a post-tetanic count: a five-second tetanus at 50 Hz, three seconds’ pause, then single stimuli at 1 Hz. The number of twitches is inversely related to depth.

If the post-tetanic count is one or two, that is a profound block and neostigmine will not reverse it — it has a ceiling, because once acetylcholinesterase is fully inhibited no further rise in junctional acetylcholine is available. The options are to wait for spontaneous recovery to at least the reappearance of T2, or to give sugammadex, which at 4 mg/kg reverses a block at this depth because it removes the drug from plasma rather than competing with it.

Whichever I choose, the endpoint is the same: a train-of-four ratio of 0.9 or more at the adductor pollicis on a calibrated objective monitor. I would not accept palpation for that, because fingers cannot reliably detect fade above a ratio of about 0.4. I would also remember that having just given a tetanus, the next few minutes of readings will overstate recovery.

Likely follow-ups

• What would a post-tetanic count of 1 tell you?
• Could you reverse this with neostigmine?
• What train-of-four ratio would satisfy you before extubation, and how would you measure it?

Neuromuscular Blockers 4: Monitoring and Reversal →

They differ fundamentally in mechanism, and everything else follows from that. Neostigmine acts indirectly: it inhibits acetylcholinesterase, junctional acetylcholine accumulates, and it outcompetes the blocker at the receptor. The blocker is still there. Sugammadex acts directly: it encapsulates aminosteroid molecules in a cyclodextrin cavity, removing them from plasma, so the drug diffuses away from the junction. It is a non-competitive antagonist and neostigmine is an indirect competitive one.

The consequences are the answer. Neostigmine has a ceiling, because once the enzyme is fully inhibited no more acetylcholine is available, so it cannot reverse a profound block and needs some spontaneous recovery first. It raises acetylcholine everywhere, so it needs an antimuscarinic — glycopyrrolate, because its onset matches. Sugammadex has no ceiling and reverses any depth, has no autonomic effects and needs no antimuscarinic. But it works only on rocuronium and vecuronium, it is expensive, it is renally cleared, and it reduces the efficacy of oral contraceptives.

After a 1.2 mg/kg rocuronium dose and a cancelled case I would give sugammadex 16 mg/kg, which is the immediate-reversal dose and the only realistic option — the block is intense, neostigmine would achieve nothing, and spontaneous recovery would take over an hour.

Likely follow-ups

• Which would you choose after a rapid sequence induction with rocuronium 1.2 mg/kg that turns out to be a cancelled case?
• What would you warn the patient about afterwards?
• Is there a situation where sugammadex is of no use at all?

Neuromuscular Blockers 4: Monitoring and Reversal →

Because its effect has a ceiling. It works by inhibiting acetylcholinesterase so acetylcholine accumulates and out-competes the relaxant. The enzyme pool is finite: once it is fully inhibited, no further acetylcholine can be recruited however much more neostigmine is given. If the relaxant still occupies most receptors, the competition cannot be won. Sugammadex has no such ceiling because it removes the relaxant instead.

Pharmacology SAQ Paper 2 · Q4 →

Nothing useful. Sugammadex encapsulates lipophilic steroidal molecules — rocuronium, vecuronium, pancuronium. Cisatracurium is a benzylisoquinolinium and does not fit the cyclodextrin cavity, so there is no reversal. That patient needs neostigmine, or time and Hofmann elimination.

Pharmacology SAQ Paper 2 · Q4 →

Because its onset more closely matches neostigmine’s, so the heart rate is smoother — atropine acts faster than neostigmine and causes an initial tachycardia followed by bradycardia as it wears off first. Glycopyrronium is also a quaternary amine and does not cross the blood–brain barrier, so it avoids central antimuscarinic effects.

Pharmacology SAQ Paper 2 · Q4 →

No. Extrajunctional acetylcholine receptor upregulation after denervation is established by then — the risk begins at roughly 24 to 72 hours — and suxamethonium could cause a fatal hyperkalaemic cardiac arrest. Use rocuronium 1.2 mg/kg, with sugammadex available if the airway is lost. Here the hyperkalaemia risk, not the intracranial pressure, decides it.

Pharmacology SAQ Paper 2 · Q4 →