2019B01 Discuss the potential adverse effects of suxamethonium.

Unsafe paralysis

· Can’t intubate, can’t oxygenate -> desaturation -> death

· Can’t protect airway -> aspiration

Histamine release

· Direct effect on mast cells. Not immune mediated.

· Degranulation of mast cells

· H1 (G_q):

o Vasodilatation, capillary leak, ↓mAP

o ↓AV node conduction, coronary vasoconstriction

o Bronchoconstriction

· H2 (G_s):

o ↑contractility, coronary vasodilatation

o Bronchodilatation

Anaphylaxis

· 1 in 2000-2500

· Similar to rocuronium

· Depends upon population

· 1^st exposure: activation of specific T cell, IgE produced by specific B cell, fixes on mast cells and basophils

· 2^nd exposure: systemic degranulation of mast cells, IgE mediated

Myalgia

· ? Due to depolarisation -> fasciculation

· Risk factors: young, muscular

· Prevention: 5% ED₉₅ non-depolarising relaxant prior (not very effective)

· Treatment: analgesia, NSAID (not very effective)

↑Intra-ocular pressure

· Depolarisation -> contraction of extraocular muscle

· ↑10cmH₂O

· Avoid in open globe injury

· Coughing during laryngoscopy causes greater ↑IOP

↑Intra-gastric pressure

· Depolarisation -> contraction of abdo wall

· ↑10cmH₂O

· But also ↑lower oesophageal sphincter tone

· Risk of GOR +/- aspiration if barrier pressure <13cmH₂O

Arrhythmia

· Sinus bradycardia, AV block, asystole

· Due to agonism at cardiac mAChR

· Risk factors: big dose >2mg/kg, young children, AV node pathology

· Rx: atropine

Hyperkalaemia

· Depolarisation -> open cation channel -> K⁺ efflux (also Na⁺ and Ca²⁺ influx)

· Normal: ↑K⁺ ~0.5mmol/L

o May be significant if renal failure with existing ↑K⁺

· Denervation: ↑↑K⁺ -> arrhythmia, cardiac arrest

o ↑ extrajunctional receptors with γ-ε substitution -> ↑channel opening time

o e.g. burns, critical illness myopathy, muscular dystrophy

o Highest risk 1 week – 3 months after onset

· ECG changes (in order)

o Repolarization abnormalities (tall T waves)

o >Atrial paralysis (small or absent P wave)

o Conduction delay (AV block, wide QRS)

o Cardiac arrest ~8-9mM (sine wave, asystole)

Suxamethonium apnoea

· Two stage metabolism by plasma cholinesterase (PChE) to inactive products

· Two alleles for PChE. Variations: normal, dibucaine-resistant (DR), fluoride-resistant, silent

· Treatment: sedate and ventilate in ICU; consider FFP or dialysis

· Follow up: testing of patient and family

Alleles	Frequency	Dibucaine number	Offset time
2 x normal	96%	80	5min
1 x normal 1 x DR	<4%	60	20-30 mins
2 x DR	0.03% 1 in 30,000	20	8 hours = sux apnoea

Masseter spasm

· ? forme fruste malignant hyperthermia, ? due to under-dosing

· Especially in children

· May impede intubation

Malignant hyperthermia

· Hypermetabolic reaction to volatile anaesthetics and suxamethonium

· Mutation in RYR1 gene encoding skeletal muscle ryanodine receptor/channel on sarcoplasmic reticulum

· Continuous Ca²⁺ release, tetany, ↑temp, rhabdo

· 80% mortality if untreated

· Specific Rx: dantrolene 1mg/kg up to 10x then infuse 24 hours

· General Rx: stop drug, sedate, intubate, ventilation, cool

· Treat complications: e.g. hyperkalaemia, arrhythmia