Systemic effects of Isoflurane

Physical properties 

Isoflurane is a halogenated ethyl methyl ether (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether) and is a geometric isomer of enflurane. Isoflurane is a clear, colourless, volatile liquid with a pungent odour. It is presented in amber-coloured bottles and requires no preservatives for storage. It is stable, does not react with metal or other substances and is non-flammable in clinical concentrations.

Uses

Maintenance of general anaesthesia.

Treatment of severe asthma in patients requiring mechanical ventilation in ICU.

Systemic effects 

RS:

 • Dose-dependent depression of ventilation with depression of the ventilatory response to carbon dioxide. • Decrease in tidal volume but an increase in ventilatory rate in the absence of opioid drugs.

 • Respiratory tract irritation and laryngospasm, making inhalational induction unfavourable.

 • Inhibition of hypoxic pulmonary vasoconstriction (thereby increasing shunt fraction). 

• Bronchial smooth muscle relaxing properties, particularly in the context of bronchoconstriction caused by histamine and acetylcholine.

CVS: 

• Dose-related reduction in MAP, primarily by reduction in systemic vascular resistance (SVR), although isoflurane also has a negatively inotropic effect. 

• Reflex tachycardia. 

• Arrhythmias are uncommon, and there is little sensitisation of the myocardium to catecholamines. 

• Coronary vasodilatation with the possibility of ‘coronary steal’. Dilatation in normal coronary arteries offers a low resistance to flow and may reduce perfusion through stenosed neighbouring vessels, causing distalischaemia. However, although this remains a theoretical concern, it does not appear to be of any clinical significance.

CNS:

 • Causes general anaesthesia and reduction in cerebral metabolic rate. 

• At concentrations >1 MAC causes cerebral vasodilatation and increases cerebral blood flow (CBF), leading to raised ICP. 

• Does not cause seizure activity on the EEG. 

• Induces dose-dependent muscle relaxation and depression of neuromuscular transmission with potentiation of non- depolarising neuromuscular blocking agents (NMBAs).

GI/GU: 

• Reduction in renal blood flow, although this is not thought to affect renal function in clinical use. 

• Uterine relaxation. 

• No effect on hepatic function or blood flow. 

• Increased risk of postoperative nausea and vomiting (PONV). 

Other: 

• Trigger for malignant hyperthermia (MH).

Pharmacology

Uptake:

 • With its relatively low blood/gas partition coefficient, alveolar and blood partial pressures equilibrate rapidly compared with older agents such as halothane but more slowly than desflurane and sevoflurane. 

• Rate of recovery is slower than that associated with desflurane or sevoflurane because of its greater solubility (higher blood/gas partition coefficient). 

Metabolism: 

• Less than 0.2% metabolised by liver (defluorination via cytochrome P450 (CYP2E1) producing hexafluoroisopropanol (HFIP)). 

Excretion: 

• Majority of the delivered drug is excreted unchanged through the lungs.

 • Less than 0.2% renal excretion; HFIP is excreted in urine after conjugation with glucuronic acid.