Methoxyflurane
Methoxyflurane
physical properties
effects on organ system
biotransformation and toxicity
contraindications
drug interactions
-MAC value: 0.16 %
-vapor pressure: 22.5 mmHg at 20 degrees celcius
-halogenated methyl ether
-colorless
-sweet, fruity odor
-light senstitive which is stabilized with butylated hydroxytoluene
-non-explosive and nonflammable at clinical concentrations
-most potent inhalational anesthetic
-high lipid solubility leading to absorption within breathing circuit and low vapor pressure reduce rate of induction with methoxyflurane
Central Nervous System
-decreases CMR02
-increases CBF
-increases ICP
Cardiovascular System
-decreases myocardial contractility
-decreases mean arterial pressure secondary to decreased myocardial contractility
-baroreceptor reflex intact which leads to increased heart rate
Respiratory System
-increased respiratory rate
-decreased tidal volume
-resultant decrease in alveolar ventilation
-elevated resting Pac02
-mild bronchodilating properties
-depressed mucociliary function
Hepatic System
-decreases hepatic blood flow
Renal System
-decreases renal blood flow
-decreases GFR
-may be associated with high-output renal failure (discussed more in detail in biotransformation and toxicity)
Neuromuscular System
-relaxes skeletal muscles
biotransformation and toxicity
-liver microsomal cytochrome P-450 enzyme activity leads to extensive metabolism of methoxyflurane
-oxidative metabolites of methoxyflurane include: free flouride ions and oxalic acid
-both flouride ions and oxalic acid are both considered to be nephrotoxic
-free flouride ions are considered responsible for the vasopressin-resistant high output renal failure
-renal toxicity from methoxyflurane is associated with: peak plasma flouride levels and duration of exposure
-flouride ions directly inhibit renal tubular function which leads to a concentrating defect within the kidneys
Clinical signs of methoxyflurane toxicity:
-polyuria resistant to administration of vasopressin
-increased serum osmolality
-increased serum sodium
-increased creatinine
-increased BUN
-decreased urinary clearance of creatinine
-decreased urinary clearance of urea nitrogen
-urine hypo-osmolality
-generally not used due to nephrotoxicity
-if used in healthy patients, exposure should be limited to less than 2 MAC hours
-patients with renal impairment should not be exposed to methoxyflurane
-nephrotoxic drugs (ex. aminoglycosides) may have additive effects leading to renal failure
-enhanced methoxyflurane metabolism with drugs such as: phenobarbital, isoniazid, and ethanol
-increased metabolism of methoxyflurane may lead to higher than expected flouride ions
-methoxyflurane prolongs the effects of nondepolarizing muscle relaxants (NDMR)
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