2019A10 Describe the effects of sevoflurane on the following regional circulations:
cerebral, coronary, pulmonary, hepatic and uteroplacental. Do not discuss specific organ effects.

 

Intro:

·         Flow physiology

·         Cellular

·         Systemic

·         Regional

 

Flow physiology:

Ohm’s law

·   Flow rate = (P1 – P2) / resistance

Poiseuille’s law

·   Resistance to laminar flow = (8 x length x viscosity) / (π x radius4)

·   Hence radius is the major factor

 

Cellular effects:

↑GABA/glycine activity

↓SNS output from medulla

·   ↓Inotropy

·   ↓Vasoconstriction

·   ↓Venoconstriction

·   Note relative preservation of baroreceptor reflex

↓L-Ca2+ activity

·   ↓Inotropy

·   ↓Vasoconstriction

·   ↓Venoconstriction

↑Nitric oxide release

·   ↓Vasoconstriction

·   ↓Venoconstriction

 

Systemic vascular effects: (dose-dependent)

Direct

·   ↓Inotropy -> ↓cardiac output

·   ↓Vasoconstriction -> ↓SVR, ↓PVR

·   ↓Venoconstriction -> ↓MSFP -> ↓preload -> ↓cardiac output

Indirect

·   Baroreceptor reflex

o ↑Heart rate -> ↑cardiac output nearer to normal

·   Excitation (Guedel’s stage 2)

o ↑SNS output -> ↑HR, ↑mAP

 

Cerebral circulation:

CBF vs CMRO2

·   Coupling impaired (not ablated) due to direct vasodilatory effect

·   Left shift and increased slope

CMRO2 vs MAC

·   Dose-dependent reduction in electrophysiological function (60% of total)

o Burst suppression at ~1.5 MAC

o Isoelectricity at ~2 MAC

·   No effect on basal function (40% of total) – only reduced by hypothermia

CBF vs MAC

·   0-0.5MAC: ↓CBF below baseline (↓CMRO2 outweighs)

·   0.5-1MAC: ↑CBF back to baseline

·   >1MAC: ↑CBF above baseline (vasodilatation outweighs)

·   Important if already raised ICP (e.g. intracranial bleed)

Other

·   Luxury perfusion: due to ↓CMRO2 but ↑CBF

·   Hypoventilation: ↑PaCO2 may cause further vasodilatation (if spont vent)

 

Coronary circulation:

Factors increasing flow

*predominant*

·   Metabolic autoregulation: ↑HR -> ↑MVO2

·   Direct vasodilatory effect

·   ↓SNS output

Factors decreasing flow

*outweighed*

·   Metabolic autoregulation: ↓SVR/wall tension, ↓contractility -> ↓MVO2

·   ↓Aortic root DBP -> ↓perfusion pressure

Coronary steal syndrome

·   Stenotic vessels are maximally dilated when awake

·   Other vessels dilate under volatile GA

·   Blood is ‘stolen’ from already threatened myocardium

·   Only relevant if steal-prone anatomy

·   More likely with isoflurane

·   Not clinically significant

Anaesthetic preconditioning

·   Mimic of ischaemic preconditioning

·   Activation of vascular (but mainly mitochondrial, sarcolemmal) K+ATP channel

·   Onset in minutes, offset 3-4 days

 

Pulmonary circulation:

Effects

·   Direct vasodilatation

·   ↓SNS output -> vasodilatation

·   ↓PVR

·   ↓Pulmonary artery pressure

Significance

·   Impaired HPV -> ↑V/Q mismatch

·   ↓PASP -> ↑alveolar dead space, ↑West zone 1

 

Hepatic circulation:

Factors increasing flow

·   Direct vasodilatation

·   ↓SNS output -> vasodilatation

Factors decreasing flow

·   ↓mAP -> ↓perfusion pressure

Significance

·   Unimportant at usual partial pressure

·   Preserved hepatic arterial buffer response (?)

 

Uteroplacental circulation:

Factors increasing flow

·   Direct vasodilatation

·   ↓SNS output -> vasodilatation

(but vessels are already maximally dilated)

Factors decreasing flow

·   ↓mAP -> ↓perfusion pressure

Significance

·   Pressure-passive circulation

·   Risk of foetal asphyxia under GA

 

 

Feedback welcome at ketaminenightmares@gmail.com