16A12: Exam Report

In relation to neuromuscular blocking drugs – Discuss the factors that influence the speed of ONSET of neuromuscular block.

38% of candidates passed this question.

The question specifically asked for factors that influenced the speed of onset of neuromuscular block. This information is different to the factors that influence neuromuscular blockade in general which was what many candidates focussed on. It was expected candidates would address the main factors known to influence the speed of onset of neuromuscular block: –
potency of the agent used (inverse relationship to speed of onset); rate of delivery of the agent to the NMJ (blood flow / muscle group); and mechanism of the neuromuscular block (non-depolarising vs depolarising).

14A09: Exam Report

Discuss the factors that may potentially influence the speed of onset of neuromuscular blockade.

16% of candidates passed this question.

Speed of onset is related to how quickly an effective  dose reaches the neuromuscular junction, the type of interaction with the receptor and the margin of safety of the receptors. Examples of parameters that increase speed of onset include a high drug rate of delivery (high CO, high muscle group blood flow, and fast injection rate), high drug concentration  (higher dose, low potency, higher ED 95, lower protein binding) or a depolarising block. A  good answer would include a list of these factors, with a brief explanation. Mention of other factors such as electrolyte disturbances gained additional marks. It was expected that the direction of an effect would be clearly indicated (e.g. & “potency” would  not score a mark unless the candidate wrote – “low potency increases speed of onset’, etc.).  These drugs are charged molecules which do not cross cell membranes and have a low volume of  distribution. Absorption from GIT, Lipid solubility, pKa, metabolism and clearance have minimal relevance to speed of onset.     

L2i / 16A12 / 14A09: Discuss the factors that may potentially influence the speed of onset of neuromuscular blockade

Mechanism of Neuromuscular Blockade

  • Blocks nAChR at NMJ
  • Onset is measured by TOF = time taken for 95% decrease of T1 for an intubating dose
  • Speed of onset depends on the speed with which 20% receptor occupancy (Depol MR) or 75% receptor occupancy (NDMR)
    • Fast = Sux, Roc
    • Intermediate = Vecuronium, Atracurium
    • Slow = Cisatracurium, Pancuronium, Mivacurium
  • Dose administered depends on the drug’s ED95 (2-3 x ED95 require to supress twitch height by 95%)

Drug Factors


NDMR require >75% receptor occupancy

High dose = greater concentration gradient = faster onset


RSI ROC = 4xED95 = 1.2mg/kg = 60sec

Intub ROC = 2xED95 = 0.6mg/kg = 120sec

Drug Potency

Lower potency means a higher dose of the drug is needed to achieve affect. 

Low affinity NMB requires high dose to achieve ED95

High affinity NMB requires low dose to achieve ED95


Cisact intub = 0.15mg/kg

Roc intub = 0.6mg/kg

Depol v NDMR

Depol MR have much faster onset


SUX 30-60sec

ROC RSI 60sec

Drug Interactions

Precurarization (priming)

Use of low dose NDMR 5 min prior will partially block the NMJ →   follow this with an intubating dose of drug will decrease time to intubating conditions

Drugs that increase potency

LA, volatiles, aminoglycosides, frusemide →   all enhance NDMR = faster onset

Drugs which improve CO

Inotropes and vasopressors which increase CO will enable the drug to reach effect site quicker, improving onset time

Drugs that affect ACh production

Corticosteroids common in ICU practice increase Ach synthesis and its spontaneous and stimulated release – delaying onset time.

Chronic steroids use decreases nAChR and increases resistance to NDMR

Patient Factors

nAChR Affinity

nAChR has 5 subunits

Strength of binding to 2x a subunits determines drug onset

In disease states

Burns/immobilisation – nAChR composed of 5 x a7 subunits, which is resistant to blockade because requires 5 subunits to be bound

Myesthenia gravis = fewer nAChR = faster onset with NDMR (slower onset sux)


Onset Young adults > elderly


Onset Women > Men


Onset Smokers > non smokers


Onset Lower plain region > High Altitude

Body Temp

Onset is delayed in hypothermina


Dose based on IBW

Poor nutrition, reduced muscular mass, increased TBW = delay onset

Electrolyte Disturbances

HypoK/Mg/Ca/Resp Acidosis = enhance onset time

Heart Failure/ Cardiogenic Shock

Reduced CO delays onset

Site of administration

CVC > Periph vein > intramuscular

Rate of injection →   faster injection bolus = faster onset

Injection site above heart = faster

Muscle Group

Drug distribution to sk m

Muscle group type:  larynx > diaph > adductor pollicis

Fast twitch have more AchR than slow twitch and thus faster onset