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

 

List:

·     ↓GFR

·     Compound A nephrotoxicity

·     Fluoride toxicity

 

↓GFR:

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

 

Compound A nephrotoxicity:

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

 

Fluoride toxicity:

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