Suxamethonium apnoea Flashcards
In what % of the population does sux have a prolonged duration of action
4%
Describe the structure of suxamethonium
Quaternary amine ester consisting of two molecules of acetylcholine joined at their non-quaternary ends.
Name the enzyme that metabolizes succinylcholine
Plasma cholinesterase
How much sux is excreted unchanged in urine
10%
What is the normal half life of sux
2- 4 minutes
Where is plasma cholinesterase synthesized
In the liver
Describe the structure of plasma cholinesterase
Four identical subunits with four catalytic sites
What causes sux apnoea
Alterations in level or efficacy of plasma cholinesterase
What can influence the activity of plasma cholinesterase?
Inherited factors (genetic polymorphism) Acquired factors - decreased availability or inhibition
What causes decreased availability of plasma cholinesterase?
DECREASED HEPATIC PRODUCTION
Severe hepatic dysfunction (Cirrhosis)
Hypothyroidism: reduces enzyme production
INCREASED DESTRUCTION Extracorporeal circulation --> increased breakdown - haemofiltration - Plasmaphoresis - Cardiac bypass
PREGNANCY
- Dilution
- Oestrogen impairs enzyme synthesis
(reduced by 20% but usually clinically insignificant)
What inhibits plasma cholinesterase and hence prolongs the effects of sux
Drugs that are either substrates or inhibitors of plasma cholinesterase will prolong the effects of sux:
- Edrophonium (Achase inhibitor)
- Neostigmine (Achase inhibitor)
- Organophosphorus compounds (insecticides) (Achase inhibitor)
- Local anaesthetic esters
Give four clinical examples of when the effects of sux may be prolonged and explain why
Pregnancy (Diluted and increase estrogen reduces synthesis of plasma cholinesterase)
Cocaine use (Cocaine is an ester local anaesthetic broken down by plasma cholinesterase - it is a substrate and therefore reduces efficacy of plasma cholinesterase from breaking down sux)
Renal dialysis (Plasma cholinesterase is destroyed by any extracorporeal circulatory procedure)
Malnutrition (Reduced production of plasma cholinesterase)
Describe the recognised gene mutations that affect the action of plasma cholinesterase. How do the different combinations affect the performance of plasma cholinesterase and hence the duration of action of SUX
Usual (u)
Atypical (a)
Fluoride (f)
Silent (s)
Normal - EuEu
3-5 min
Heterozygous - EuEa, EuEf, EuEs
5-30 min
Homozygous - EaEa, EsEs, EfEf
2-8 h
How is atypical cholinesterase activity tested for in vitro?
The Dibucaine number
What is the Dibucaine number?
Plasma cholinesterase is combined with substrate benzylcholine to produce a light emitting reaction.
Dibucaine is added. Dibucaine inhibits this reaction normally reducing light production. With an abnormal enzyme –> light production will not be significantly reduced
Dibucaine number 80 (EuEu) - normal - duration of sux 3 - 5 mins
Dibucaine number 20 (EaEa) - very abnormal duration sux 2 - 8 hours
Fluoride is used to detect the abnormal fluoride gene –> Fluoride number
No inhibition occurs with either dibucaine or fluoride if the patient is homozygous for the ‘silent’ gene .
How is SUX apnoea recognized
Suspicion: if patient does not require non-depolarizing muscle relaxant
Awareness
- Sweating, lacrimation, dilated pupils
- Minimal / irregular / jerking respiratory effort
SNS
- HPT
- Tachycardia
- Intermittent desaturation
How can the diagnosis of sux apnoea be confirmed?
Peripheral nerve stimulator
- Train of four twitch response: No response or equal reduction in strength for all four twitches
( Four normally strong twitches would indicate the patient has fully recovered from the neuromuscular block.)
What is the differential diagnosis for postoperative apnoea
PHARMACOLOGICAL
Residual anaesthetic agent
Excess opioid effect
Inadequately reversed non-depolarizing neuromuscular block
PHYSIOLOGICAL Hypo or hypercapnoea Severe electrolyte abnormality Severe metabolic acidosis Intracranial pathology Severe hypothermia
Describe the management of suxamethonium apnoea
- IPPV –> Oxygenation and ventilation (normocapnoea)
- Sedation –> prevent awareness - use volatile or intravenous anaesthetic agents
- Maintenance fluids, temperature
Continue until the nerve stimulator demonstrates return of normal muscle strength or the patient make adequate respiratory effort.
Council patient and family
Take clotted blood for plasma cholinesterase activity, dibucaine and fluoride numbers
Communicate: GP, referral letter, test relatives and provide Medic alert
Discuss treatment of patients with SUX apnoea with FFPs
The principle is that FFPs should contain plasma cholinesterase and might speed up the recovery in SUX apnoea.
However, the amount of plasma cholinesterase in each FFP is significantly variable and the effect unpredictable –> also there are potential infection and immunological risks when transfusing blood products
What is the difference between a patient recovering from a depolarizing neuromuscular block versus a non-depolarizing neuromuscular block using the peripheral nerve stimulator
Depolarizing block - No fade. Equal amplitude twitches –> all twitches lower amplitude than normal
Non-depolarizing block - Fade is demonstrated.
What are the side effects of succinylcholine
Related to the agonist effects on nicotinic and muscarinic AChRs
- Myalgia
- Cardiac dysrhythmias
- Hyperkalaemia (burns/rhabdo/denervation/UMND)
- Transient increase IOP
- Increased intragastric pressure with increased LES tone
- Increased intracranial pressure
- Hx malignant hyperthermia is absoulte CI
How does succinylcholine cause cardiac dysrhythmias
GANGLIONIC stimulation
- Tachycardia and increased BP may be caused by ganglionic stimulation with an overall increase SNS to the heart
CARDIAC MUSCARINIC stimulation
- Stimulation of cardiac M receptors may lead to sinus bradycardia, junctional rhythm or even asystole
- Particularly in children (PreRx with atropine) or adults with repeated sux exposure within 5 minutes.
How does succinylcholine cause hyperkalaemia, how significant is this rise in potassium and when is this clinically significant
Mechanism of hyperkalaemia
- SCh exaggerates transmembrane ion flux leading to a rise in serum K+ of 0.5 to 1.0 mEq/L
However, life threatening rise in serum potassium can occur in the following conditions due to either/or proliferation of extrajunctional AChRs and/or damaged muscle membranes and a massive potassium release upon stimulation
- Major burns (avoid SUX for 2 years)
- Massive tissue injury
- Extensive denervation of skeletal muscle
- UMN disease
Patients with mild elevations in K+ related to renal failure may safely receive sux
How can side effects to sux be reduced
PreRx with NDNMB – Cisatracurium 1mg IV or Rocuronium 3mg IV 2 to 4 minutes before SCh –> may blunt visible fasciculations but is not uniformly effective at attenuating all other side effects
Awake patients receiving NDNMB –> diplopia/weakness/dyspnoea.
If pretreating in RSI –> give increased dose of SUX 1.5mg/kg
What are the two different phases of neuromuscular blockade caused by succinylcholine
PHASE 1 BLOCKADE - Because SCh is not degraded by AChE as rapidly as ACh, it persistently depolarizes the motor endplate, leading to inactivation of the voltage-gated sodium channels in the perijunctional zone that are necessary for propagation of the depolarization.
- Transient muscle fasciculations followed by relaxation
- Absence of ‘fade’ to tetanic or TOF stimulation
- Presence of post-tetanic potentiation (PTP)
- AChE inhibitors potentiate rather than reverse the block.
PHASE 2 BLOCKADE is most likely to occur after repeated or continuous administration of SCh when the total dose exceeds 3 to 5 mg/kg. Phase II blockade is thought to be secondary to repeated channel opening, causing distortion of the normal electrolyte balance and desensitizing the junctional membrane to further depolarization. It has some of the characteristics of a nondepolarizing blockade:
- Fade after tetanic of TOF stimulation
- Presence of PTP
- Tachyphylaxis (increasing dose requirement)
- Prolonged recovery
- Partial or complete reversal by AChE inhibitors
