2015A07 Briefly outline the effects of sevoflurane on skeletal, smooth and cardiac muscle tissues.
Include how these effects are mediated and their clinical significance.

 

Intro:

·     Sevoflurane: relevant cellular effects

·     Cardiac muscle

·     Smooth muscle

·     Skeletal muscle

 

Sevoflurane: relevant cellular effects

·       ↑activity at GABA-A and glycine receptors -> Cl- influx -> prevent action potential

·       ↓L-Ca2+ activity (↓L-Ca2+)

·       ↑nitric oxide release (↑NO)

·       ↓medullary sympathetic outflow (↓SNS)

·       ↓nicotinic ACh receptor activity (↓nAChR)

·       Most effects are dose-dependent

 

Cardiac muscle:

Contractility

Heart rate

·    Direct effect: ↓

o ↑GABA/glycine -> ↓SNS output from medulla

o ↓L-Ca2+ channel activity, ↓Ca2+ sensitivity

·    Indirect effect: ↑

o Baroreceptor reflex relatively preserved

o Reflex tachycardia common

Anaesthetic preconditioning

·    Activates ATP-sensitive K+ channels in mitochondria and sarcolemma

·    Mimics ischaemic preconditioning -> ↓risk myocardial ischaemia

·    Active at MAC >0.25

·    Onset in minutes, offset 3-4 days

↑QT interval

·    ? Mechanism

·    ↑Risk torsades de pointes (rarely significant)

·    Sevoflurane, enflurane, isoflurane

Coronary steal syndrome

·    ↓ L-Ca2+ channel -> SVR

·    Awake:

o Stenotic vessel maximally dilated

o Other vessels mid-dilated

o Preserved flow through stenosis

·    Under GA:

o Stenotic vessel no change

o Other vessels ↑dilatation

o ↓CO, ↓SVR -> ↓aortic root diastolic pressure -> ↓total coronary flow

o ↓flow through stenosis

·    Unproven theoretical concern

·    Isoflurane > others due to greater reduction in SVR

 

Smooth muscle:

Mechanism

·    ↓L-Ca2+, ↓SNS

Systemic vasodilatation

·    Arteries: ↓SVR, ↓mAP; ↑heat loss

·    Veins: ↓preload -> cardiac output; easier to cannulate

Pulmonary vasodilatation

·    ↓PVR, ↓HPV, ↑V/Q mismatch, ↓PaO2

Cerebral vasodilatation

·    Overrides ↓CMRO2 at >1MAC

·    Risk of ↑ICP concomitant intracranial pathology

Bronchodilatation

·    ↓Airway resistance

·    Used in status asthmaticus

Uterine relaxation

·    ↑Bleeding during GA Caesarean (hence supplement with N2O, propofol)

 

Skeletal:

Mechanism

·    CNS and α-motor neurons: ↑GABA-A, ↑glycine

·    Pre-synaptic: ↓L-Ca2+ -> ↓ACh release

·    Post-synaptic: ↓nAChR

Immobility

·    Potentiates paralytics

·    Facilitates surgery

Hypoventilation

·    Relaxation of intercostals > diaphragm

·    Depression of chemoreceptors and respiratory centre

·    ↓↓Response to ↓PaO2

·    ↓Response to ↑PaCO2

Airway obstruction

·    ↓Pharyngeal dilator tone

·    Need for airway device

Malignant hyperthermia

·    Rare, life-threatening hypermetabolic reaction to volatile anaesthetics or suxamethonium

·    Mutation in RYR1 gene encoding skeletal muscle ryanodine receptor

·    Continuous Ca2+ release from SR causing continuous contraction

·    Idiosyncratic, not dose-dependent like all the above