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:

Central

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

·  ↓Inotropy

·  ↓Vasoconstriction

·  ↓Venoconstriction

·  Note relative preservation of baroreceptor reflex

Peripheral

·  ↓L-Ca2+ activity, ↓SR Ca2+ release

·  ↑KATP activity

·  ↑NO 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

·  Dose-dependent vasodilatation

·  Coupling of CBF and CMRO2 impaired (not ablated)

·  Slope ∝ dose -> greater effect at high dose

 

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

·  Exponential decay -> greater effect at low dose

 

CBF vs MAC***

·  At low concentration: indirect vasoconstriction (via ↓CMRO2) wins

·  At high concentration: direct vasodilation wins

·  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

·  Due to activation of K+ATP channel (vascular/mitochondrial/sarcolemma)

·  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

 

 

 

Addendum***

·       This graph is from Miller’s Anesthesia, Chapter 11

·       The data are from Anesthesiology (https://pubmed.ncbi.nlm.nih.gov/3740503/)

·       At 0.5 MAC, mean values for local blood flow were reduced in every grey matter tissue

·       However, none of the individual changes was statistically significant due to a large standard deviation

·       My personal opinion is:

o   It is unlikely that a universal decrement in mean blood flow between 0 MAC and 0.5 MAC was due to chance

o   Statistical significance would have been reached had sample sizes been larger

o   These findings are consistent with the curves for CBF vs CMRO2 and CMRO2 vs MAC

·       The alternative opinion is:

o   There is no evidence for significant change in CBF between 0 MAC and 1 MAC

o   In this range, the indirect vasoconstriction (via ↓CMRO2) and the direct vasodilation roughly cancel each other out

o   This is consistent with the leftward/upward shift in the CBF vs mAP curve that occurs with any concentration of volatile anaesthetic

o   See the Eger-Stoelting version below:

 

 

Special thanks to Dr. Stan Tay for his insights.