Isoflurane

Isoflurane :

• Difluromethyle ether isomer of Enflurane
• Ross Terrell – 1965 (Ohio) W.C. Stevens – 1971
•  Before 1980 Isoflurane considered to produce carcinogenesis  

Physical properties:

• Clear colorless gas, 
• non-inflammable, 
• Slightly pungent smell 
• Stable does not react with metal and other substance 
• MAC is 1.15% in oxygen 
• MAC is 0.56% in nitrous oxide 
• Blood/gas solubility co-effecient 1.4 
• Oil/gas solubility coeff. = 98

Metabolism :

• 0.17% of the absorbed dose is metabolized
• Metabolism take place in the liver by oxidation to difluromethanole and trifluro-acitic acid
•  Difluromethanole further metabolized into formic acid and fluoride ions
• Because of minimal metabolism a small amount free fluoride serum concentration
• Free fluoride is neprotoxic     

Action on respiratory system :

• Dose dependent respiratory depression
• Decrease tidal volume 
• But increase respiratory rate in the absence of opioids
• Due to pungent smell it causes respiratory irritation thus make inhalational induction with Isoflurane is difficult
• Blunt the normal ventilatory response to hypoxia and hypercarbia  

Action on cardiovascular system:

• Slightly decrease myocardial contractility 
• Slightly decrease cardiac out put 
• Systematic hypotension is due to decrease systemic vascular resistance 
• Arrhythmias is uncommon
• Little sensitization of myocardium to catecholamine's
• In addition to dilating system arterioles isoflurane cause coronary vasodilatation produce coronary steel syndrome  
• Coronary steel syndrome “dilating of the normal arterioles offer low resistance to blood flow may reduce perfusion through stenosed neighboring vessels 
• Increased heart rate because of partial preservation of carotid baro-reflex  

Uterus and placenta :

• Produce uterine muscle relaxation
• Decrease placental blood flow which depend upon cardiac out put 
• Due to uterine relaxation increase the incidence of post partum hemorrhage  

Action on CNS :

• CNS depression 
• Low concentration of isoflurane does not causes any change in cerebral blood flow at normocapnia
• High concentration of isoflurane increase cerebral blood flow which increase intracranial pressure
• it high concentration of 2 MAC reduce cerebral metabolic oxygen requirement

Hepato-renal action:

• Total hepatic blood flow is reduce 
• Hepatic oxygen supply is better maintained with isoflurane than halothane 
• Liver function test is usually not effected 
• Isoflurane decrease renal blood flow
• Decrease glamorous filtration rate and urinary out put  

Action on muscle :

• Isoflurane dose dependent decrease of neuromuscular transmission (muscle relaxation)
• It potentiate the action of non-depolarizing muscle blocking agent 

 
Advantages:

• Rapid action
• Decreases blood loss
• Little risk of  PONV
• No hepatotoxicty, nephrotoxicity
• Useful in conditions with raised ICP
• No convulsive activity
• Negligible shivering post-op
• Rapid recovery 

Disadvantages:

• Breath-holding
• Respiratory depression
• Animal studies – Fetal asphyxia
• Trigger malignant hyperthermia