Suxamethonium Flashcards
What class of drug is suxamethonium?
Suxamethonium is a depolarising neuromuscular blocking agent.
What is the structure of suxamethonium?
Suxamethonium is made up of two molecules of acetylcholine, joined by an acetyl group bond.
Each acetylcholine molecule contains an ester bond.
(CH3)3 N+ CH2 CH2 O C=O CH2 -
CH2 C=O O CH2 CH2 N+ (CH3)3
Tell me about the presentation and uses of suxamethonium.
Is it an odourless, colourless solution that should be stored in the fridge at 4’C. In the UK, it is available as a chloride in 2ml ampoules of 50mg/ml. The dosage is 1-2mg/kg intravenously, or 4mg/kg intramuscularly.
Predominantly it is used for rapid sequence induction and for short surgical procedures or electroconvulsive therapy.
What is the mechanism of action and kinetics of suxamethonium?
Suxamethonium acts on the nicotinic acetylcholine receptor on the post-synaptic membrane of the neuromuscular junction.
It causes depolarisation, and subsequent prevention of transmission of further action potentials.
It has a short duration of action of 3-5 minutes, and is hydrolysed by plasmacholinesterase to succinic acid and choline. Only 10% is excreted in the urine.
What are the characteristics of a partial depolarising block?
A depolarising block is also described as a phase 1 block. It is characterised by equal but reduced twitch height with train of four count and a single pulsed stimulation, and it causes a sustained but reduced tetanic contraction with no fade or post-tetanic potentiation.
Following administration of large doses of suxamethonium, a phase 2 block may occur, whereby features of non-depolarising blockade gradually replace that of depolarising blockade.
The mechanism of phase 2 block is uncertain, but may involve pre- or post- junctional receptor modulation.
Please list the side effects of suxamethonium.
(8)
(In order of common to rare:)
- Myalgia - most frequently seen in young females
- Cardiac arrhythmias - sinus or nodal bradycardia, or ventricular in origin. Most commonly seen in paediatrics and with a second dose.
- Hyperkalaemia - in normal individuals, a transient increase of 0.5mmol/L occurs. This may be enough to cause arrhythmias / cardiac arrest in those with a high K+ to start with, or those with renal failure.
- Increased intra-occular pressure - may be increased by 10-15mmHg transiently. It should be used in caution with penetrating globe injuries. Concurrent administration of thiopentone is said to offset this rise in intra-occular pressure.
- Intragastric pressure - rises by about 10cmH2O, but is offset by an increase in the lower oesophageal sphincter tone
- Anaphylaxis
- Suxamethonium apnoea
- Malignant hyperpyrexia
What are the contraindications of suxamethonium?
Hyperkalaemia
Severe muscle trauma
History of malignant hyperpyrexia History of suxamethonium apnoea
History of anaphylaxis to suxamethonium
24 hours to 18 months post burns >10% BSA or spinal cord trauma
Avoided in patients with muscle disease if at all possible
What is malignant hyperpyrexia / hyperthermia / MH?
MH is a life-threatening autosomal dominant condition which occurs only in susceptible individuals, and is triggered by volatile anaesthetics and suxamethonium.
It results from uncontrolled skeletal muscle metabolism.
It is important to be able to recognise promptly, as left unrecognised it can quickly progress to circulatory collapse and death.
What are the features of MH
The classic features of MH are masseter spasm and muscle rigidity, a rising temperature of >2’C per hour, and a rising end tidal CO2.
The first sign of MH may be an unexplained tachycardia, so it is important to have a high index of suspicion. As oxygen demand outstrips supply, hypoxia will occur.
Blood results will typically show elevated levels of serum K+, Ca2+, creatine kinase, and myoglobin. As MH progresses a metabolic acidosis will develop, often followed by acute renal failure.
How is MH managed?
As in all emergency situations, I would declare the emergency and ask for surgery to be safely halted, call for help, give 100% oxygen, and take a structured A-E assessment of the patient, treating serious or life-threatening problems as they are found.
Specific to malignant hyperthermia, the triggering agent should be withdrawn immediately. Dantrolene should be given as soon as possible. Supportive treatment including aggressive cooling, correction of acidosis, respiratory support with hyperventilation, and inotropic support as required. Hyperkalaemia, acute renal failure, and disseminated intravascular coagulation should be treated as required. The patient should be transferred to intensive care and treated until complete resolution of symptoms. Anaesthesia should be maintained throughout.
What is Dantrolene and how does it work?
Dantrolene is a muscle relaxant that works by uncoupling the excitation-contraction process, preventing Ca2+ release from the sarcoplasmic reticulum in skeletal muscle.
The dose in MH is 2-3mg/kg, repeated up to 10mg/kg.
It is available in 20mg vials containing mannitol and sodium hydroxide, which are dissolved in 60ml water for use.
It is laborious to reconstitute, so may helpers will be needed.
Since its introduction, the mortality of MH has reduced from 90% to 10%.
What is the pathophysiology of MH?
MH is caused by a mutation on the ryanidine receptor, which is located on the sarcoplasmic reticulum and plays a crucial role in calcium control.
What tests are available to confirm MH
The caffeine-halothane contracture is the diagnostic of choice. A biopsied piece of muscle is subjected to 2% halothane and caffeine, and the tension in the muscle is measured. Contracture occurs in susceptible muscle, and patients are labelled ‘susceptible’, ‘equivocal’, or ‘non-susceptible’.
Tests should be carried out in all suspected cases and immediate relatives.
What is suxamethonium apnoea?
Suxamethonium apnoea is prolonged blockade following suxamethonium administration, in a patient with decreased plasma cholinesterase activity.
It can result from genetic variability, or acquired conditions. Acquired deficiency results from liver or cardiac failure, renal disease, pregnancy, thyrotoxicosis, malnutrition, burns, following plasmaphoresis, or drugs which inhibit cholinesterases.
Tell me more about genetic causes of sux apnoea.
Enzymatic activity is altered by single amino-acid substitutions.
Several autosomal recessive genes have been identified, and the degree of enzymatic inihibition by dibucaine and fluoride has been used to describe the genetic variations.
There are 4 alleles described:
- usual, also known as normal
- atypical, also known as dibucaine resistant
- fluoride resistant
- silent
96% of the population are homozygote for the normal gene, with full enzyme function.
0.001% are homozygote for the silent gene, with no enzyme function.
Dibucaine and fluoride numbers denote the percentage of inhibition. The higher the number, the better the enzyme function.
In homozygotes for the silent and atypical gene, paralysis can last for 4 hours.
In homozygotes for the fluoride resistant gene, paralysis can last 2 hours.
Heterozygotes with abnormal genes make up approximately 4% of the population, and exhibit mildly prolonged paralysis of up to 10 minutes.
