Neuromuscular Blockade

BT_GS 1.35 Describe the physiology of the neuromuscular junction and the mechanism of action of neuromuscular blocking agents
BT_GS 1.36 Describe the pharmacokinetics of neuromuscular blocking agents
BT_GS 1.37 Describe the pharmacological differences between neuromuscular blocking agents and the clinical importance of these differences.

T / F  rocuronium is less potent than vecuronium – this explains its faster onset *

T / F  the usual intubating dose of a non-depolarising blocker is referred to as the ED95 – for vecuronium, it is 0.1 mg/kg

T / F  the diaphragm and laryngeal muscles are more resistant to non-depolarising block than the adductor pollicis, yet their onset of block occurs faster than at the adductor pollicis **

T / F  the elimination of rocuronium is 10-20% renal and >70% hepatic

T / F  vecuronium has active metabolites, but rocuronium does not

T / F  blockade of pre-junctional NACh receptors prevents ACh being made available fast enough to sustain tetanic or repeated (e.g. TOF) contraction – this explains “fade”

* can you explain why?
** can you explain your answer?

Miller 8th edition, Chapter 34

2018.2 SAQ 4 – Compare and contrast the pharmacology of suxamethonium and rocuronium

BT_GS 1.36  Describe the pharmacokinetics of neuromuscular blocking agents
BT_GS 1.37  Describe the pharmacological differences between neuromuscular blocking agents, and the clinical significance of these differences

Another “core” SAQ! The level of detail needed to answer this question is understandably high, as you would expect in a specialist anaesthetics exam.

The best reference is Miller.

T / F  the ED95 for suxamethonium is 1 mg/kg, and for rocuronium is 0.6 mg/kg

T / F  train of four can be used to assess the depth of block produced by both suxamethonium and rocuronium

T / F  suxamethonium can trigger MH, but rocuronium does not

T / F  patients with myasthenia gravis are resistant to suxamethonium, but very sensitive to rocuronium

T / F  Suxamethonium is metabolised by plasma cholinesterase, to succinyl monocholine and choline. Rocuronium is metabolised in the liver – the main metabolite is 17, desacetyl-rocuronium, which is mainly excreted in the bile.

T / F  the duration of paralysis with suxamethonium is 5-10 minutes. This increases to 1-2 hours in people who are homozygous atypical for the plasma cholinesterase gene

T / F  Suxamethonium has some affinity for muscarinic ACh receptors, which can cause bradycardia. Rocuronium has no affinity for MAChR’s.

T / F  (taken from NAP 6 Report, page 4)  suxamethonium was almost twice as likely to cause anaphylaxis as any other NMBA, with a rate of 11.1 per 100,000 administrations


We use scientific terminology, classifications, and nomenclature, every day of our working lives. Often, we don’t pause to consider the layers of meaning behind these words.

What is a steroid?

The term “steroid” is used in connection with many things – corticosteroids, sex steroids, aminosteroids, cholesterol. We hear of illicit “steroids” being taken – what are they? Various “cortisone” containing preparations also come under the same umbrella.

So, what is a steroid? Before reading any further, look this up. You should look up both the chemical structure, and a definition in words.

Having done that, you should now appreciate how a steroid “backbone” can be used as the framework for many different molecules, because a vast array of different side chains can be added to the steroid core.

Which of the following drugs contains a steroid moiety?

T/F  hydrocortisone

T/F  vecuronium

T/F  digoxin

T/F  thyroxine

T/F  atracurium

Curare was the first neuromuscular blocking agent introduced into clinical use. But it is a benzylisoquinolone. To read a bit about the development of pancuronium, the first aminosteroid used clinically, click Brown_et_al-1997-Anaesthesia. This article should help you appreciate the key structure-activity relationships which were permitted by using a steroid core.

Now that the term “benzylisoquinolone” has been brought up, you are no doubt eagerly wondering what it really means. Apart from the neuromuscular blockers, what other drugs share this basic structure?

2018.1 SAQ 12 Neostigmine and sugammadex

Compare and contrast the pharmacology of neostigmine and sugammadex

“Anaesthesia reversal”, as these drugs are referred to on an automated theatre record we used to use, has always stuck me as a funny term – I hope I never have an anaesthetic where either of these two drugs is sufficient to reverse it! These are drugs we give on a daily basis, although sugammadex is used rarely in the institution I work in because of the cost. Is that its only limitation?

You should find these drugs covered adequately in the  pharmacology books on the reading list

BT_GS 1.39 Describe the reversal of neuromuscular blockade using anti- cholinesterase agents, anticholinergics and sugammadex and the physiological effects of reversal

Both neostigmine and sugammadex will reverse all aminosteriod non depolarising muscle relaxants T/F

Sugammadex can be used safely in patients with severe renal impairment (eGFR < 30ml/min) T/F

Unlike neostigmine, sugammadex has no effect on acetylcholine T/F

In a patient with a TOF ratio ≥ 2, equipotent doses of sugammadex and neostigmine with have a similar time to onset of effect T/F

There is a significant risk of oral contraceptive pill failure in patients who have received sugammadex T/F

BT_GS 1.35 Describe the physiology of the neuromuscular junction and the mechanism of action of neuromuscular blocking agents

If you’ve done anaesthesia for burns patients then you’ll know there is one drug that you must not forget to not give! Less dramatic, but perhaps more important because of the larger number of patients affected, are stroke, critical illness or any prolonged immobility (good reason for regular breaks from study).


Prolonged immobility results in increased sensitivity to suxamethonium   TRUE/FALSE

Prolonged immobility results in decreased sensitivity to NMDRs   TRUE/FALSE

Prolonged immobility results in increased expression of ‘”immature” AChR isoforms   TRUE/FALSE

Immature AChR isoforms are more sensitive to ACh   TRUE/FALSE

The presynaptic AChR are mostly of the immature type   TRUE/FALSE

BT_GS 1.35 Describe the physiology of the neuromuscular junction and the mechanism of action of neuromuscular blocking agents

This is well-covered in Hemmings and Egan (Chapter 18). Giving neuromuscular blockers is one of the most risk-filled components of anaesthetic practice, so it’s worth knowing a bit more than how to draw a nice picture of the NMJ and the top 10 side-effects of suxamethonium…

Each muscle fibre is innervated by a single unmyelinated branch of a myelinated motor axon   TRUE/FALSE

Nicotinic receptors are sparse in the depths of the synaptic clefts of the post-junctional membrane   TRUE/FALSE

The perijunctional membrane has a high density of voltage-gated sodium channels   TRUE/FALSE

The number of quanta of Ach released is not affected by the extracellular calcium ion concentration   TRUE/FALSE

Each nerve impulse releases at least 200 quanta, each of about 5000 ACh molecules   TRUE/FALSE

The difference between the depolarisation caused by Ach and the threshold level needed to trigger an action potential is called the ‘safety factor’   TRUE/FALSE

Patient of the week – 2


Another piece for the V&A, this made entirely from cutlery (I am drawing a long bow for today’s post)

Here is another case in this sporadic series

Some months ago I looked after a young patient who had been retrieved following a machete injury near the shoulder, resulting in almost total amputation of the arm. The injury had occurred some hours previously, with the patient left at the side of the road.

He had been intubated by the retrieval team at the scene.

On arrival to the Emergency Department his potassium level was 6.5 mmol/L

BT_GS 1.38

Normal serum potassium rise following an intubating dose of suxamethonium is 1.5mmol/L TRUE/FALSE

BT_PO 1.72

ECG changes associated with hyperkalaemia include tall peaked T waves and a shortened PR interval. TRUE/FALSE

He was taken to theatre to reattach the arm. He was hypovolaemic and anuric.

I set about trying to lower his serum potassium and restore his blood volume.

BT_PO 1.40

Salbutamol may be detected as halothane when nebulised within the circle circuit TRUE/FALSE

BT_PO 1.72

Calcium gluconate is used in the  management of hyperkalaemia as it lowers serum potassium TRUE/FALSE

BT_RT 1.9

Hyperkalaemia and hypercalcaemia are potential metabolic consequences of massive transfusion    TRUE/FALSE

To be honest, nothing I tired (and I tried a lot of everything I could think of, short of starting dialysis) lowered his potassium at all. But at least it didn’t increase any further. He survived the reimplantation  and was transferred to ICU for further management, including some much needed haemodialysis.

BT GS 1.36 Describe the PK of neuromuscular blocking agents


Regarding rocuronium:

It is a more potent agent than vecuronium   T/F

If you drank it, it would paralyse you eventually         T/F

Its duration of action is dependent on what time of the day you administer it    T/F

It commonly causes stinging when injected*    T/F

It is presented as a racemic mixture                 T/F


*Read this paper for a description of what it feels like to have rocuronium and suxamethonium injected when you are wide awake.  Response of the bispectral index to neuromuscular block in awake volunteers. P Schuller et al. British Journal of Anaesthesia 2015; 115(Supp 1): i95-103.

Reading any clinical paper about rocuronium should allow you to answer the third question. Unfortunately, reading any of the recommended texts for the exam won’t be enlightening about this particular property of rocuronium.

2017.1 : SAQ 6

Discuss the potential adverse effects of suxamethonium

BT_GS 1.38

This is a drug with a cornucopia of adverse effects, know them so you know when not to use the drug, and what to be alert for every time you do use it.

Hyperkalaemia is more likely with a repeat dose  TRUE/FALSE

Bradycardia is more likely with a repeat dose  TRUE/FALSE

Prolonged paralysis is more common in South East Asians than Caucasians  TRUE/FALSE

Myalgia is more likely in a patient who has a spinal cord injury  TRUE/FALSE

Masseter spasm can be an early sign of MH  TRUE/FALSE