2019A Question 10
Describe the effects of sevoflurane on the following regional circulations: Cerebral, coronary, pulmonary, hepatic and uteroplacental. Do not discuss specific organ effects.
Examiner Report
19.9 % of candidates achieved a pass in this question.
To pass this question required correct identification of the effect of sevoflurane on the regional circulations without major errors. As per Ohm’s law the effect on regional blood flow is dependent on both the perfusion pressure as well as regional vascular resistance. At anaesthetic concentrations of sevoflurane, autoregulation is preserved in all of these regional circulations except for the uteroplacental unit.
Pleasingly, many candidates recognised that the placental circulation is already maximally dilated so high dose sevoflurane may decrease uteroplacental flow due to a decrease in systemic perfusion pressure. Sevoflurane causes dose dependent vasodilatation. The majority of candidates recognised this effect but few could describe the mechanism. Very few candidates noted that the effects of sevoflurane on all these regional circulations at anaesthetic doses are modest and of little clinical concern in the healthy individual. Most candidates described effects that may be seen at doses above one MAC which was still an acceptable answer.
Common errors were: Answers that focused on systemic circulatory effects; not addressing all the circulations; and discussing organ effects eg uterine tone. In their discussion of coronary blood flow candidates invariably used the incorrect term ischaemic preconditioning as opposed to volatile or anaesthetic preconditioning - they are not the same thing but share a similar mechanism. Marks were not deducted for this minor terminology error, however.
Model Answer
Structure:
- Flow physiology
- Cellular
- Systemic
- Regional
Flow Physiology
| Law | Detail |
|---|---|
| Ohm’s Law | |
| Poiseuille's Law | - Hence radius is the major factor |
Cellular Effects
| Factor | Detail |
|---|---|
| ↑ 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
| Factor | Detail |
|---|---|
| Direct | - ↓ Inotropy → ↓ Cardiac output - ↓ Vasoconstriction → ↓ SVR, ↓ PVR - ↓ Venoconstriction → ↓ MSFP → ↓ Preload → ↓ Cardiac Output |
| Indirect | - Baroreceptor reflex - ↑ Heart rate → ↑ Cardiac output nearer to normal - Excitation (Guedel’s stage 2) |
Cerebral Circulation
| Factor | Detail |
|---|---|
| CBF vs CMRO2 | - Dose-dependent vasodilatation (↓ L-Ca2+ activity, ↑ NO activity) - 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) - Burst suppression at ~1.5 MAC - 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
| Factor | Detail |
|---|---|
Factors ↑ flow (predominantly) |
- Metabolic autoregulation: ↑ HR → ↑ MVO2 - Direct vasodilatory effect - ↓ SNS output |
Factors ↓ 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
| Factor | Detail |
|---|---|
| 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
| Factor | Detail |
|---|---|
| Factors ↑ flow | - Direct vasodilatation - ↓ SNS output → Vasodilatation |
| Factors ↓ flow | - ↓ MAP → ↓ Perfusion pressure |
| Significance | - Unimportant at usual partial pressure - Preserved hepatic arterial buffer response |
Uteroplacental Circulation
| Factor | Detail |
|---|---|
| Factors ↑ flow | - Direct vasodilatation - ↓ SNS output → Vasodilatation (but vessels are already maximally dilated) |
| Factors ↓ flow | - ↓ MAP → ↓ Perfusion pressure |
| Significance | - Pressure-passive circulation - Risk of foetal asphyxia under GA |
Footnotes
- From the Maekawa et al paper: At 0.5 MAC, mean values for local blood flow were reduced in every grey matter tissue
- However, none of the individual changes are statistically significant due to a large standard deviation
- One interpretation:
- An alternative interpretation:
- There is no evidence for significant change in CBF between 0 MAC and 1 MAC
- In this range, the indirect vasoconstriction (via ↓ CMRO2) and the direct vasodilation roughly cancel each other out
- This is consistent with the leftward/upward shift in the CBF vs MAP curve that occurs with any concentration of volatile anaesthetic
- See the Eger-Stoelting version below
Special thanks to Dr. Stan Tay for his insights.
References
- Miller RD, Eriksson LI, Fleisher LA, Weiner-Kronish JP, Cohen NH, Young WL. Miller's Anaesthesia. 8th Ed (Revised). Elsevier Health Sciences.
- Maekawa, Tsuyoshi, Concezione Tommasino, Harvey M. Shapiro, Jayne Keifer-Goodman, and Robert W. Kohlenberger. Local Cerebral Blood Flow and Glucose Utilization during Isoflurane Anesthesia in the Rat. Anesthesiology 65, no. 2 (1 August 1986): 144–51.