1999A14 Briefly outline the pharmacological effects of the volatile anaesthetic agents on the kidneys.

Cardiovascular causes

·   ↓L-Ca²⁺ activity, ↑nitric oxide release, ↓medulla SNS outflow

·   ↓Preload, ↓contractility, ↓cardiac output, ↓SVR -> ↓mAP

·   If mAP <70: failure of myogenic autoregulation -> ↓RBF, ↓GFR, ↓urine output

·   Partly offset by baroreceptor response -> ↑HR

Hormonal causes

·   ↓RAAS activity

o ↓SNS output -> ↓β₁ activation -> ↓renin release

·   ↓ANP release

o ↓SNS / ↓L-Ca²⁺ / ↑NO -> venodilatation -> ↓CVP

Origin

·   Sevo + CO₂ absorber -> compounds A-E

·   Compound A = pentafluoroisopropenylfluoromethyl ether

Risk factors

·   Baralyme > Sodalime >Amrisorb > Litholime

·   Fresh absorbent

·   ↑% sevoflurane

·   ↓FGF rate

·   ↑temp

Toxicity

·   Predicted threshold in man: ?200ppm

·   Levels observed in practice: 20-40ppm (β-lyase pathway 30x less active cf. rats)

·   Recommendation: FGF >2L/min, ↓2MAC hours if FGF 1-2L/min

Methoxyflurane

·   70% metabolized (since high BGPC)

·   Mostly renal CYP2E1 -> inorganic and organic F

·   Causes high output renal failure

·   Threshold 50mcg/mL, occurs at 2MAC hours

Sevoflurane

·   2-5% metabolized (since low BGPC)

·   Large amount of fluoride production, but hepatic > renal