Neuromuscular blocking agents Flashcards
When is neuromuscular blockade indicated?
- Endotracheal Intubation
- Surgery where muscle relaxation is essential
- Mechanical ventilation
What are the risks of incomplete reversal of neuromuscular blockade
- Very unpleasant for patient
- Hypoxia
- Aspiration
What can be used to reduced the risk of incomplete reversal of neuromuscular blockade?
Peripheral Nerve Stimulator
What is the premise of standard induction (versus RSI)
During standard induction the NDMR should only be administered once it has been confirmed that the airway can be maintained using simple mask ventilation
If the patient then proves impossible to intubate after being paralyzed, simple mask ventilation may be used to keep the patient oxygenated and anaesthetized.
What is the premise of RSI (versus standard induction)
Indicated in situations where the patient is at risk of aspiration of gastric contents.
Preoxygenation
Induction agent + depolarizing neuromuscular blocker
WITHOUT CHECKING FOR MASK VENTILATION
Sux wears off within a few minutes –>allowing spontaneous respiration to restart. The alveolar reservoir of oxygen should limit any hypoxia until spontaneous respiration restarts
When is maintenance of muscle paralysis indicated?
Surgery where muscle relaxation is essential
Mechanical ventilation in the ICU when lung compliance is low
Can repeated doses of non-depolarizing agent be administered during the surgery or in ICU to maintain paralysis?
If standard induction was used with a non-depolarizing muscle relaxant then repeated doses of the same agent can be used to maintain paralysis –> exact dose and frequency should be guided by the response to a nerve stimulator
Why should a peripheral nerve stimulator be used before administration of a non-depolarising muscle relaxant after SUX was used for RSI?
To ensure sux has worn off. If sux has not worn off, there is a possibility that succinylcholine apnoea is present.
If PNS is not used and paralysis is prolonged, it would be unclear which agent is responsible.
What is succinylcholine apnoea
Genetically abnormal plasma cholinesterase –> prolonged effects of this enzyme –>much slower metabolism of succinylcholine
What are the intubation and maintenance doses for vecuronium
Intubation dose: 0.1 mg/kg
Maintenance: 1 - 2 mg (Depends on PNS)
What is the intubating dose and maintenance dose of atracurium
Intubation: 0.5 mg/kg
Maintenance: 10 - 20 mg (Depends on PNS)
What is the intubating dose for succinylcholine
1 - 2 mg/kg
Can SUX be used to maintain neuromuscular blockade?
No
How does succinylcholine work?
Structurally related to acetylcholine –> produces muscle relaxation by first activating muscle fibres, then preventing a further response–> muscle fasciculation
What metabolizes succinylcholine?
Plasma pseudocholinesterase
What are the patient related and clinical contra-indications to the use of succinylcholine
Patient related contraindications: 1. Malignant hyperthermia 2. Anaphylaxis to succinylcholine 3. Succinylcholine apnoea (these conditions can still be triggered for the first time)
Clinical contraindications:
- Widespread denervation injury –> especially after burns/spinal cord injury
- Open, penetrating eye injury
Why is widespread denervation injury a clinical contra-indication?
During repolarization, K+ moves down its concentration gradient via nicotinic receptors into the extracellular environment. Normal rise in plasma potassium is about 0.5mmol rise which is clinically insignificant.
Burns/spinal cord injury –> disuse of muscle fibres with associated upregulation and proliferation of junctional and extrajunctional post-synaptic Ach nicotnic receptors. This leads to a more significant rise in plasma K+ –> VF –> asystole
Why is an open eye-injury a contra-indication to the use of succinylcholine
Contraction of the extra-ocular muscles following the use of succinylcholine result in a significant rise in intraocular pressureso that the contents of the eyeball may be compromised when there is an open eye injury
What are the adverse effects if SUX
- Bradycardia (especially after 2nd dose)
- ‘Sux’ pains
- Transient raised pressure in eye, stomach, cranium
What is the mechanism for bradycardia most common after a second dose of SUX and how is this prevented
The structural similarity of SUX to Ach –> cardiac muscarinic receptor stimulation –> bradycardia.
Prevention: pre-administration of an anti-cholinergic: atropine/glycopyrrolate
What are “sux pains”
Unco-ordinated muscle fasciculations –> pains in the jaw and neck most common
Persist for a day or two and are most likely in women
How do Non-depolarising neuromuscular blockers work?
These are all competitive antagonists of acetylcholine at the NMJ
What is the classification of non-depolarising muscle relaxants and what is this based on ?
Based on their structure:
Aminosteroids
- Vecuronium
- Rocuronium
- Pancuronium
Benzylisoquinoliniums
- Atracurium
- Cisatracurium
- Mivacurium
When is atracurium avoided and when is atracurium the agent of choice?
Avoided: asthmatics
- Histamine release (usually local but can be systemic) BS in asthma + VD and low BP possible
Favourable in hepatic/renal failure
- organ-independent metabolism
(Hofmann degradation and ester hydrolysis)
How is atracurium metabolized?
In an organ independent manner:
Hofmann degradation
- spontaneous breakdown of atracurium into laudanosine and acrylate (inactive in humans) –> temperature dependent (MUST BE KEPT IN FRIDGE)
Ester hydrolysis
- By non-specific esterases which are distinct from plasma cholinesterase
Describe the metabolism of Vecuronium
Metabolized in the liver and excreted in bile and urine.
Prolonged effects with hepatic and renal dysfunction.
Phenytoin/CBZ - induce liver enzymes –> higher doses required.
PNS can accurately guide use
What proportion of the nicotinic receptors should be occupied by the non-depolarising muscle relaxant to produce blockade?
90%
Only a small proportion of the receptors need by activated by Ach to trigger contraction - presence of spare receptors at the NMJ ensures a large margin of safety for signal transduction from nerve to muscle
What effect does neostigmine have at the NMJ?
Achase inhibition leading to increased concentration of Ach to compete more successfully with the NDNMB and so restore normal muscle function
Neostigmine acts at all sites where AchE is present and this includes the heart –> what effect might this have
Excessive stimulation of Muscarinic receptors. In the heart this would lead to a bradycardia
What can be used to prevent muscarinic stimulation (and bradycardia) caused by the AchE inhibitor neostigmine
M receptor blocker: Atropine.Glycopyrrolate
Dose: Succinylcholine Rocuronium Vecuronium Atracurium
Succinylcholine: 1 - 2 mg/kg
Rocuronium: 0.6 - 1.2 mg/kg
Vecuronium: 0.1 mg/kg (Maintain: 1 - 2 mg PNS)
Atracurium: 0.5mg/kg (Maintain: 10 -20 mg PNS)
What dose of neostigmine + glycopyrrolate is required for reversal of neuromuscular blockade
Neostigmine 0.05 mg/kg
Glycopyrrolate: 0.2mg/1mg Neostigmine
0.2mg/5mg Pyridostigmine
Describe the presentation of neostigmine
1ml ampoule with 2.5 mg neostigmine
OR
1ml ampoule with 2.5 mg neostigmine with 0.5mg glycopyrrolate
List 4 uses of the Peripheral Nerve Stimulator
- Have effects of SUX worn off prior to maintenance dose of non-depolarizing NMB
- Check the depth of NMB
- Determine that NMB is reversible
- Confirm NMB is reversed
What is the Train of Four?
The Train of Four describes four supramaximal stimuli, each with a uration of 0.1 msec, delivered at 2 Hz
Frequency = 2Hz (2 cycles per second)
Duration of each stimulus: 0.1 msec
Period: 2 seconds
What is the Train of Four count (TOFC)
This is the number of twitches
Gives a guide to the depth of non-depolarizing block
4 twitches: 0 - 85 % receptors occupied 3 twitches: 90% receptors occupied 2 twitches: 92% receptors occupied 1 Twitch: 95% receptors occupied 0 twitch: ~100%
What is the typical current required to produce a supramaximal stimulus
> 60mA is sufficient
What is the TOF ratio?
This is the ratio of the fourth twitch height to the first twitch height: T4:T1
How is the TOF ratio interpreted?
As the non-depolarising NMB wears off the TOF ratio approaches 1 i.e. T4 approximates the amplitude of T1
Name 3 commonly used types of nerve stimulation
- TOF
- The Double burst
- Tetany
Define threshold current, maximal current, supramaximal current
Threshold current: amplitude necessary to evoke a muscle contraction
Maximal current: amplitude necessary to evoke contraction in all fibres of the muscle
Supramaximal current: amplitude 30% greater than the amplitude of the maximal current to ensure consistent contraction of all fibres despite changes in resistance over time
Why is it ideal to monitor the adductor pollicus muscle
The adductor pollicus muscle is the only muscle in the thenar eminence innervated solely by the ulnar nerve. Monitoring this muscle helps to ensure that the muscle contraction is generated by a nerve impulse rather than by direct muscle stimulation.
Describe placement of electrodes for peripheral nerve stimulation of the ulnar nerve whilst monitoring the adductor pollicus nerve
Place stimulating electrodes on the anterior surface of the forearm along the ulnar nerve. Distal negative electrode 2 cm proximal to the wrist and the proximal positive electrode 5 cm proximal to the negative electrode.
Describe electrode placement for peripheral nerve stimulation of the posterior tibial nerve whilst monitoring the function of the flexor hallicus muscle (plantar flexion of the big toe)
Place electrodes posterior to the medial malleolus along the posterior tibial nerve to monitor planter flexion of the first toe.
What is tetany
A constant stimulus to the nerve at 50Hz
How can a response to tetany be interpreted?
Before a neuromuscular blockers is given, and after it has been properly reversed, the muscle contraction has NO FADE.
In which situations is tetany used?
- During profound block, when no response is seen to TOF, the presence of post-tetanic facilitation, in particular the number of twitches elicited, helps to determine the time until the return of the TOF response and hence the time before reversal of blockade is possible.
- To check that the block has been reversed adequately –> NO FADE
What % receptors and hence TOF count is required in the majority of operations?
no more than 90% occupancy by NMB agent.
2 - 3 twitches
What TOF count is required for gastric surgery and why?
TOF = 0 as the diaphragm is resistant to NMB. A TOFC of 1 there may be diaphragm movement which may interfere with gastric surgery.
What are the consequences if reversal of NMB is attempted prematurely
The degree of muscle power regained may not be adequate - residual postoperative paralysis.
When should reversal be completed by
Prior to the patient regaining consciousness
What does any degree of fade represent
Incomplete reversal
Does breathing indicate adequate reversal?
No
Is subjective visual assessment of muscle twitches to a PNS reliable
No
What 3 actions help reduce residual neuromuscular blockade during recovery?
- Use NMB sparingly
- Always reverse neuromuscular blockade by a non-depolarizing muscle relaxant
- Always use a PNS when using NMBs
True or false: the duration of action of atracurium is increased in the presence of a magnesium infusion
True
True or false: Acidosis prolongs NMB by vecuronium
True
When can NMB reversal be attempted?
When 3 twitches are present
Does SUX produce fade?
No
